Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway.
Identifieur interne : 000293 ( Main/Exploration ); précédent : 000292; suivant : 000294Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway.
Auteurs : Yujie Bao [République populaire de Chine] ; Jiayin Tang [République populaire de Chine] ; Yun Qian [République populaire de Chine] ; Tiantian Sun [République populaire de Chine] ; Huimin Chen [République populaire de Chine] ; Zhaofei Chen [République populaire de Chine] ; Danfeng Sun [République populaire de Chine] ; Ming Zhong [République populaire de Chine] ; Haoyan Chen [République populaire de Chine] ; Jie Hong [République populaire de Chine] ; Yingxuan Chen [République populaire de Chine] ; Jing-Yuan Fang [République populaire de Chine]Source :
- Cell death & disease [ 2041-4889 ] ; 2019.
Descripteurs français
- KwdFr :
- ARN long non codant (génétique), ARN long non codant (métabolisme), Bacteroides fragilis (pathogénicité), Biologie informatique (MeSH), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Petit ARN interférent (génétique), Protéine homologue de Ras enrichie dans le cerveau (génétique), Protéine homologue de Ras enrichie dans le cerveau (métabolisme), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme), Technique de Western (MeSH), Tumeurs colorectales (génétique), Tumeurs colorectales (microbiologie), Tumeurs colorectales (métabolisme), microARN (métabolisme).
- MESH :
- génétique : ARN long non codant, Petit ARN interférent, Protéine homologue de Ras enrichie dans le cerveau, Sérine-thréonine kinases TOR, Tumeurs colorectales.
- microbiologie : Tumeurs colorectales.
- métabolisme : ARN long non codant, Protéine homologue de Ras enrichie dans le cerveau, Sérine-thréonine kinases TOR, Tumeurs colorectales, microARN.
- pathogénicité : Bacteroides fragilis.
- Biologie informatique, Humains, Lignée cellulaire tumorale, Technique de Western.
English descriptors
- KwdEn :
- Bacteroides fragilis (pathogenicity), Blotting, Western (MeSH), Cell Line, Tumor (MeSH), Colorectal Neoplasms (genetics), Colorectal Neoplasms (metabolism), Colorectal Neoplasms (microbiology), Computational Biology (MeSH), Humans (MeSH), MicroRNAs (metabolism), RNA, Long Noncoding (genetics), RNA, Long Noncoding (metabolism), RNA, Small Interfering (genetics), Ras Homolog Enriched in Brain Protein (genetics), Ras Homolog Enriched in Brain Protein (metabolism), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , genetics : RNA, Long Noncoding, RNA, Small Interfering, Ras Homolog Enriched in Brain Protein, TOR Serine-Threonine Kinases.
- chemical , metabolism : MicroRNAs, RNA, Long Noncoding, Ras Homolog Enriched in Brain Protein, TOR Serine-Threonine Kinases.
- genetics : Colorectal Neoplasms.
- metabolism : Colorectal Neoplasms.
- microbiology : Colorectal Neoplasms.
- pathogenicity : Bacteroides fragilis.
- Blotting, Western, Cell Line, Tumor, Computational Biology, Humans.
Abstract
Long noncoding RNAs (lncRNAs) contribute to many steps in carcinogenesis and often serve as biomarkers or therapeutic targets for tumor diagnosis and therapy. Although the role of lncRNAs in tumor formation is becoming clear, whether lncRNAs mediate gut microbiota-induced colorectal cancer (CRC) is largely unknown. Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis. BFAL1 was highly expressed in CRC tissues compared with that in adjacent normal tissues. In vitro, BFAL1 was upregulated in ETBF-treated CRC cells. Mechanistically, ETBF promoted tumor growth via BFAL1 by activating the Ras homolog, which is the MTORC1 binding/mammalian target of the rapamycin (RHEB/mTOR) pathway. Furthermore, BFAL1 regulated RHEB expression by competitively sponging microRNAs miR-155-5p and miR-200a-3p. Clinically, both high expression of BFAL1 and high abundance of ETBF in CRC tissues predicted poor outcomes for patients with CRC. Thus, BFAL1 is a mediator of ETBF-induced carcinogenesis and may be a potential therapeutic target for ETBF-induced CRC.
DOI: 10.1038/s41419-019-1925-2
PubMed: 31515468
PubMed Central: PMC6742644
Affiliations:
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Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Tiantian" sort="Sun, Tiantian" uniqKey="Sun T" first="Tiantian" last="Sun">Tiantian Sun</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Huimin" sort="Chen, Huimin" uniqKey="Chen H" first="Huimin" last="Chen">Huimin Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Zhaofei" sort="Chen, Zhaofei" uniqKey="Chen Z" first="Zhaofei" last="Chen">Zhaofei Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Danfeng" sort="Sun, Danfeng" uniqKey="Sun D" first="Danfeng" last="Sun">Danfeng Sun</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Ming" sort="Zhong, Ming" uniqKey="Zhong M" first="Ming" last="Zhong">Ming Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Haoyan" sort="Chen, Haoyan" uniqKey="Chen H" first="Haoyan" last="Chen">Haoyan Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Jie" sort="Hong, Jie" uniqKey="Hong J" first="Jie" last="Hong">Jie Hong</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yingxuan" sort="Chen, Yingxuan" uniqKey="Chen Y" first="Yingxuan" last="Chen">Yingxuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Fang, Jing Yuan" sort="Fang, Jing Yuan" uniqKey="Fang J" first="Jing-Yuan" last="Fang">Jing-Yuan Fang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China. jingyuanfang@sjtu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31515468</idno><idno type="pmid">31515468</idno><idno type="doi">10.1038/s41419-019-1925-2</idno><idno type="pmc">PMC6742644</idno><idno type="wicri:Area/Main/Corpus">000200</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000200</idno><idno type="wicri:Area/Main/Curation">000200</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000200</idno><idno type="wicri:Area/Main/Exploration">000200</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway.</title><author><name sortKey="Bao, Yujie" sort="Bao, Yujie" uniqKey="Bao Y" first="Yujie" last="Bao">Yujie Bao</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizhaoju Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Infectious Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizhaoju Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Jiayin" sort="Tang, Jiayin" uniqKey="Tang J" first="Jiayin" last="Tang">Jiayin Tang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qian, Yun" sort="Qian, Yun" uniqKey="Qian Y" first="Yun" last="Qian">Yun Qian</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Tiantian" sort="Sun, Tiantian" uniqKey="Sun T" first="Tiantian" last="Sun">Tiantian Sun</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Huimin" sort="Chen, Huimin" uniqKey="Chen H" first="Huimin" last="Chen">Huimin Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Zhaofei" sort="Chen, Zhaofei" uniqKey="Chen Z" first="Zhaofei" last="Chen">Zhaofei Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Danfeng" sort="Sun, Danfeng" uniqKey="Sun D" first="Danfeng" last="Sun">Danfeng Sun</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Ming" sort="Zhong, Ming" uniqKey="Zhong M" first="Ming" last="Zhong">Ming Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Haoyan" sort="Chen, Haoyan" uniqKey="Chen H" first="Haoyan" last="Chen">Haoyan Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Jie" sort="Hong, Jie" uniqKey="Hong J" first="Jie" last="Hong">Jie Hong</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yingxuan" sort="Chen, Yingxuan" uniqKey="Chen Y" first="Yingxuan" last="Chen">Yingxuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Fang, Jing Yuan" sort="Fang, Jing Yuan" uniqKey="Fang J" first="Jing-Yuan" last="Fang">Jing-Yuan Fang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China. jingyuanfang@sjtu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell death & disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bacteroides fragilis (pathogenicity)</term><term>Blotting, Western (MeSH)</term><term>Cell Line, Tumor (MeSH)</term><term>Colorectal Neoplasms (genetics)</term><term>Colorectal Neoplasms (metabolism)</term><term>Colorectal Neoplasms (microbiology)</term><term>Computational Biology (MeSH)</term><term>Humans (MeSH)</term><term>MicroRNAs (metabolism)</term><term>RNA, Long Noncoding (genetics)</term><term>RNA, Long Noncoding (metabolism)</term><term>RNA, Small Interfering (genetics)</term><term>Ras Homolog Enriched in Brain Protein (genetics)</term><term>Ras Homolog Enriched in Brain Protein (metabolism)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN long non codant (génétique)</term><term>ARN long non codant (métabolisme)</term><term>Bacteroides fragilis (pathogénicité)</term><term>Biologie informatique (MeSH)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Petit ARN interférent (génétique)</term><term>Protéine homologue de Ras enrichie dans le cerveau (génétique)</term><term>Protéine homologue de Ras enrichie dans le cerveau (métabolisme)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Technique de Western (MeSH)</term><term>Tumeurs colorectales (génétique)</term><term>Tumeurs colorectales (microbiologie)</term><term>Tumeurs colorectales (métabolisme)</term><term>microARN (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Long Noncoding</term><term>RNA, Small Interfering</term><term>Ras Homolog Enriched in Brain Protein</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>MicroRNAs</term><term>RNA, Long Noncoding</term><term>Ras Homolog Enriched in Brain Protein</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN long non codant</term><term>Petit ARN interférent</term><term>Protéine homologue de Ras enrichie dans le cerveau</term><term>Sérine-thréonine kinases TOR</term><term>Tumeurs colorectales</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Tumeurs colorectales</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN long non codant</term><term>Protéine homologue de Ras enrichie dans le cerveau</term><term>Sérine-thréonine kinases TOR</term><term>Tumeurs colorectales</term><term>microARN</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Bacteroides fragilis</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Bacteroides fragilis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Blotting, Western</term><term>Cell Line, Tumor</term><term>Computational Biology</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biologie informatique</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Technique de Western</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Long noncoding RNAs (lncRNAs) contribute to many steps in carcinogenesis and often serve as biomarkers or therapeutic targets for tumor diagnosis and therapy. Although the role of lncRNAs in tumor formation is becoming clear, whether lncRNAs mediate gut microbiota-induced colorectal cancer (CRC) is largely unknown. Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis. BFAL1 was highly expressed in CRC tissues compared with that in adjacent normal tissues. In vitro, BFAL1 was upregulated in ETBF-treated CRC cells. Mechanistically, ETBF promoted tumor growth via BFAL1 by activating the Ras homolog, which is the MTORC1 binding/mammalian target of the rapamycin (RHEB/mTOR) pathway. Furthermore, BFAL1 regulated RHEB expression by competitively sponging microRNAs miR-155-5p and miR-200a-3p. Clinically, both high expression of BFAL1 and high abundance of ETBF in CRC tissues predicted poor outcomes for patients with CRC. Thus, BFAL1 is a mediator of ETBF-induced carcinogenesis and may be a potential therapeutic target for ETBF-induced CRC.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31515468</PMID><DateCompleted><Year>2020</Year><Month>08</Month><Day>31</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>11</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-4889</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>9</Issue><PubDate><Year>2019</Year><Month>09</Month><Day>12</Day></PubDate></JournalIssue><Title>Cell death & disease</Title><ISOAbbreviation>Cell Death Dis</ISOAbbreviation></Journal><ArticleTitle>Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway.</ArticleTitle><Pagination><MedlinePgn>675</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41419-019-1925-2</ELocationID><Abstract><AbstractText>Long noncoding RNAs (lncRNAs) contribute to many steps in carcinogenesis and often serve as biomarkers or therapeutic targets for tumor diagnosis and therapy. Although the role of lncRNAs in tumor formation is becoming clear, whether lncRNAs mediate gut microbiota-induced colorectal cancer (CRC) is largely unknown. Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis. BFAL1 was highly expressed in CRC tissues compared with that in adjacent normal tissues. In vitro, BFAL1 was upregulated in ETBF-treated CRC cells. Mechanistically, ETBF promoted tumor growth via BFAL1 by activating the Ras homolog, which is the MTORC1 binding/mammalian target of the rapamycin (RHEB/mTOR) pathway. Furthermore, BFAL1 regulated RHEB expression by competitively sponging microRNAs miR-155-5p and miR-200a-3p. Clinically, both high expression of BFAL1 and high abundance of ETBF in CRC tissues predicted poor outcomes for patients with CRC. Thus, BFAL1 is a mediator of ETBF-induced carcinogenesis and may be a potential therapeutic target for ETBF-induced CRC.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bao</LastName><ForeName>Yujie</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Infectious Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizhaoju Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Jiayin</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-2510-6448</Identifier><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qian</LastName><ForeName>Yun</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Tiantian</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Huimin</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Zhaofei</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Danfeng</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhong</LastName><ForeName>Ming</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Haoyan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yingxuan</ForeName><Initials>Y</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-1883-7736</Identifier><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Jing-Yuan</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China. jingyuanfang@sjtu.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>09</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cell Death Dis</MedlineTA><NlmUniqueID>101524092</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D035683">MicroRNAs</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C490211">RHEB protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D062085">RNA, Long Noncoding</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D034741">RNA, Small Interfering</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000076205">Ras Homolog Enriched in Brain Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001441" MajorTopicYN="N">Bacteroides fragilis</DescriptorName><QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015179" MajorTopicYN="N">Colorectal Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019295" MajorTopicYN="N">Computational Biology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035683" MajorTopicYN="N">MicroRNAs</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D062085" MajorTopicYN="N">RNA, Long Noncoding</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D034741" MajorTopicYN="N">RNA, Small Interfering</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076205" MajorTopicYN="N">Ras Homolog Enriched in Brain Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>02</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>08</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>08</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31515468</ArticleId><ArticleId IdType="doi">10.1038/s41419-019-1925-2</ArticleId><ArticleId IdType="pii">10.1038/s41419-019-1925-2</ArticleId><ArticleId IdType="pmc">PMC6742644</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Bao, Yujie" sort="Bao, Yujie" uniqKey="Bao Y" first="Yujie" last="Bao">Yujie Bao</name></noRegion><name sortKey="Bao, Yujie" sort="Bao, Yujie" uniqKey="Bao Y" first="Yujie" last="Bao">Yujie Bao</name><name sortKey="Chen, Haoyan" sort="Chen, Haoyan" uniqKey="Chen H" first="Haoyan" last="Chen">Haoyan Chen</name><name sortKey="Chen, Huimin" sort="Chen, Huimin" uniqKey="Chen H" first="Huimin" last="Chen">Huimin Chen</name><name sortKey="Chen, Yingxuan" sort="Chen, Yingxuan" uniqKey="Chen Y" first="Yingxuan" last="Chen">Yingxuan Chen</name><name sortKey="Chen, Zhaofei" sort="Chen, Zhaofei" uniqKey="Chen Z" first="Zhaofei" last="Chen">Zhaofei Chen</name><name sortKey="Fang, Jing Yuan" sort="Fang, Jing Yuan" uniqKey="Fang J" first="Jing-Yuan" last="Fang">Jing-Yuan Fang</name><name sortKey="Hong, Jie" sort="Hong, Jie" uniqKey="Hong J" first="Jie" last="Hong">Jie Hong</name><name sortKey="Qian, Yun" sort="Qian, Yun" uniqKey="Qian Y" first="Yun" last="Qian">Yun Qian</name><name sortKey="Sun, Danfeng" sort="Sun, Danfeng" uniqKey="Sun D" first="Danfeng" last="Sun">Danfeng Sun</name><name sortKey="Sun, Tiantian" sort="Sun, Tiantian" uniqKey="Sun T" first="Tiantian" last="Sun">Tiantian Sun</name><name sortKey="Tang, Jiayin" sort="Tang, Jiayin" uniqKey="Tang J" first="Jiayin" last="Tang">Jiayin Tang</name><name sortKey="Tang, Jiayin" sort="Tang, Jiayin" uniqKey="Tang J" first="Jiayin" last="Tang">Jiayin Tang</name><name sortKey="Zhong, Ming" sort="Zhong, Ming" uniqKey="Zhong M" first="Ming" last="Zhong">Ming Zhong</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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