miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells
Identifieur interne : 000E92 ( Ncbi/Merge ); précédent : 000E91; suivant : 000E93miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells
Auteurs : Wei Liu ; Dongdong Jiang ; Fangyi Gong ; Yumin Huang ; Yongjun Luo ; Yuluo Rong ; Jiaxing Wang ; Xuhui Ge ; Chengyue Ji ; Jin Fan ; Weihua CaiSource :
- Cell Death & Disease [ 2041-4889 ] ; 2020.
Abstract
Osteosarcoma (OS) is a malignant bone tumor which occurs mainly in adolescents with frequent pulmonary metastasis and a high mortality rate. Accumulating evidence has indicated that microRNAs (miRNAs) play a vital role in various tumors by modulating target genes as well as signal pathways, and aberrant expression of miRNAs may contribute to OS progression. This study aimed to determine the association between miR-210-5p expression and OS progression and to investigate its potential underlying mechanism. Using reverse transcription-polymerase chain reaction (RT-PCR), miR-210-5p was found to be upregulated in clinical OS specimens and cell lines. Further functional analysis demonstrated that miR-210-5p promoted epithelial–mesenchymal transition (EMT) and induced oncogenic autophagy. Luciferase reporter assay, RNA-ChIP, and western blot analysis confirmed that PIK3R5, an essential regulator in the AKT/mTOR signaling pathway, is a target downstream gene of miR-210-5p. Overexpression or knockdown of PIK3R5 reversed the functional role of overexpression or knockdown of miR-210-5p, respectively. Silencing autophagy-related gene 5 (ATG5) abolished the functional effects of miR-210-5p upregulation or PIK3R5 knockdown in OS cells. In vivo, miR-210-5p overexpression promoted OS tumor growth and pulmonary metastasis. Taken together, our results demonstrated that miR-210-5p promoted EMT and oncogenic autophagy by suppressing the expression of PIK3R5 and regulating the AKT/mTOR signaling pathway. Therefore, inhibition of miR-210-5p may represent a promising treatment for OS.
Url:
DOI: 10.1038/s41419-020-2270-1
PubMed: 32024814
PubMed Central: 7002725
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells</title><author><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Jiang, Dongdong" sort="Jiang, Dongdong" uniqKey="Jiang D" first="Dongdong" last="Jiang">Dongdong Jiang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Gong, Fangyi" sort="Gong, Fangyi" uniqKey="Gong F" first="Fangyi" last="Gong">Fangyi Gong</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Huang, Yumin" sort="Huang, Yumin" uniqKey="Huang Y" first="Yumin" last="Huang">Yumin Huang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Luo, Yongjun" sort="Luo, Yongjun" uniqKey="Luo Y" first="Yongjun" last="Luo">Yongjun Luo</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rong, Yuluo" sort="Rong, Yuluo" uniqKey="Rong Y" first="Yuluo" last="Rong">Yuluo Rong</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Wang, Jiaxing" sort="Wang, Jiaxing" uniqKey="Wang J" first="Jiaxing" last="Wang">Jiaxing Wang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Ge, Xuhui" sort="Ge, Xuhui" uniqKey="Ge X" first="Xuhui" last="Ge">Xuhui Ge</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Ji, Chengyue" sort="Ji, Chengyue" uniqKey="Ji C" first="Chengyue" last="Ji">Chengyue Ji</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Fan, Jin" sort="Fan, Jin" uniqKey="Fan J" first="Jin" last="Fan">Jin Fan</name><affiliation><nlm:aff 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type="wicri:Area/Ncbi/Merge">000E92</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells</title><author><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Jiang, Dongdong" sort="Jiang, Dongdong" uniqKey="Jiang D" first="Dongdong" last="Jiang">Dongdong Jiang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Gong, Fangyi" sort="Gong, Fangyi" uniqKey="Gong F" first="Fangyi" last="Gong">Fangyi Gong</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Huang, Yumin" sort="Huang, Yumin" uniqKey="Huang Y" first="Yumin" last="Huang">Yumin Huang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Luo, Yongjun" sort="Luo, Yongjun" uniqKey="Luo Y" first="Yongjun" last="Luo">Yongjun Luo</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rong, Yuluo" sort="Rong, Yuluo" uniqKey="Rong Y" first="Yuluo" last="Rong">Yuluo Rong</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Wang, Jiaxing" sort="Wang, Jiaxing" uniqKey="Wang J" first="Jiaxing" last="Wang">Jiaxing Wang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Ge, Xuhui" sort="Ge, Xuhui" uniqKey="Ge X" first="Xuhui" last="Ge">Xuhui Ge</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Ji, Chengyue" sort="Ji, Chengyue" uniqKey="Ji C" first="Chengyue" last="Ji">Chengyue Ji</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Fan, Jin" sort="Fan, Jin" uniqKey="Fan J" first="Jin" last="Fan">Jin Fan</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Cai, Weihua" sort="Cai, Weihua" uniqKey="Cai W" first="Weihua" last="Cai">Weihua Cai</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Osteosarcoma (OS) is a malignant bone tumor which occurs mainly in adolescents with frequent pulmonary metastasis and a high mortality rate. Accumulating evidence has indicated that microRNAs (miRNAs) play a vital role in various tumors by modulating target genes as well as signal pathways, and aberrant expression of miRNAs may contribute to OS progression. This study aimed to determine the association between miR-210-5p expression and OS progression and to investigate its potential underlying mechanism. Using reverse transcription-polymerase chain reaction (RT-PCR), miR-210-5p was found to be upregulated in clinical OS specimens and cell lines. Further functional analysis demonstrated that miR-210-5p promoted epithelial–mesenchymal transition (EMT) and induced oncogenic autophagy. Luciferase reporter assay, RNA-ChIP, and western blot analysis confirmed that PIK3R5, an essential regulator in the AKT/mTOR signaling pathway, is a target downstream gene of miR-210-5p. Overexpression or knockdown of PIK3R5 reversed the functional role of overexpression or knockdown of miR-210-5p, respectively. Silencing autophagy-related gene 5 (ATG5) abolished the functional effects of miR-210-5p upregulation or PIK3R5 knockdown in OS cells. In vivo, miR-210-5p overexpression promoted OS tumor growth and pulmonary metastasis. Taken together, our results demonstrated that miR-210-5p promoted EMT and oncogenic autophagy by suppressing the expression of PIK3R5 and regulating the AKT/mTOR signaling pathway. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cell Death Dis</journal-id><journal-id journal-id-type="iso-abbrev">Cell Death Dis</journal-id><journal-title-group><journal-title>Cell Death & Disease</journal-title></journal-title-group><issn pub-type="epub">2041-4889</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32024814</article-id><article-id pub-id-type="pmc">7002725</article-id><article-id pub-id-type="publisher-id">2270</article-id><article-id pub-id-type="doi">10.1038/s41419-020-2270-1</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Liu</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Jiang</surname><given-names>Dongdong</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Gong</surname><given-names>Fangyi</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Huang</surname><given-names>Yumin</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Luo</surname><given-names>Yongjun</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Rong</surname><given-names>Yuluo</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jiaxing</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Ge</surname><given-names>Xuhui</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Ji</surname><given-names>Chengyue</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Jin</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Cai</surname><given-names>Weihua</given-names></name><address><email>caiwhspine@sina.com</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Orthopaedics,</institution><institution>the First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, Jiangsu 210029 China</aff></contrib-group><pub-date pub-type="epub"><day>5</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2020</year></pub-date><volume>11</volume><issue>2</issue><elocation-id>93</elocation-id><history><date date-type="received"><day>12</day><month>10</month><year>2019</year></date><date date-type="rev-recd"><day>14</day><month>1</month><year>2020</year></date><date date-type="accepted"><day>16</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Osteosarcoma (OS) is a malignant bone tumor which occurs mainly in adolescents with frequent pulmonary metastasis and a high mortality rate. Accumulating evidence has indicated that microRNAs (miRNAs) play a vital role in various tumors by modulating target genes as well as signal pathways, and aberrant expression of miRNAs may contribute to OS progression. This study aimed to determine the association between miR-210-5p expression and OS progression and to investigate its potential underlying mechanism. Using reverse transcription-polymerase chain reaction (RT-PCR), miR-210-5p was found to be upregulated in clinical OS specimens and cell lines. Further functional analysis demonstrated that miR-210-5p promoted epithelial–mesenchymal transition (EMT) and induced oncogenic autophagy. Luciferase reporter assay, RNA-ChIP, and western blot analysis confirmed that PIK3R5, an essential regulator in the AKT/mTOR signaling pathway, is a target downstream gene of miR-210-5p. Overexpression or knockdown of PIK3R5 reversed the functional role of overexpression or knockdown of miR-210-5p, respectively. Silencing autophagy-related gene 5 (ATG5) abolished the functional effects of miR-210-5p upregulation or PIK3R5 knockdown in OS cells. In vivo, miR-210-5p overexpression promoted OS tumor growth and pulmonary metastasis. Taken together, our results demonstrated that miR-210-5p promoted EMT and oncogenic autophagy by suppressing the expression of PIK3R5 and regulating the AKT/mTOR signaling pathway. Therefore, inhibition of miR-210-5p may represent a promising treatment for OS.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Bone cancer</kwd><kwd>Autophagy</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China (National Science Foundation of China)</institution></institution-wrap></funding-source><award-id>81974335</award-id><principal-award-recipient><name><surname>Cai</surname><given-names>Weihua</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100004608</institution-id><institution>Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)</institution></institution-wrap></funding-source><award-id>BK20181490</award-id><principal-award-recipient><name><surname>Cai</surname><given-names>Weihua</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100010014</institution-id><institution>Six Talent Peaks Project in Jiangsu Province (Six Talent Peaks Project in Jiangsu Province of China)</institution></institution-wrap></funding-source><award-id>TD-SWYY-010</award-id><principal-award-recipient><name><surname>Cai</surname><given-names>Weihua</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100007452</institution-id><institution>Ministry of Health of China | Wu Jieping Medical Foundation</institution></institution-wrap></funding-source><award-id>320-2745-16-117</award-id><principal-award-recipient><name><surname>Cai</surname><given-names>Weihua</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Cai, Weihua" sort="Cai, Weihua" uniqKey="Cai W" first="Weihua" last="Cai">Weihua Cai</name><name sortKey="Fan, Jin" sort="Fan, Jin" uniqKey="Fan J" first="Jin" last="Fan">Jin Fan</name><name sortKey="Ge, Xuhui" sort="Ge, Xuhui" uniqKey="Ge X" first="Xuhui" last="Ge">Xuhui Ge</name><name sortKey="Gong, Fangyi" sort="Gong, Fangyi" uniqKey="Gong F" first="Fangyi" last="Gong">Fangyi Gong</name><name sortKey="Huang, Yumin" sort="Huang, Yumin" uniqKey="Huang Y" first="Yumin" last="Huang">Yumin Huang</name><name sortKey="Ji, Chengyue" sort="Ji, Chengyue" uniqKey="Ji C" first="Chengyue" last="Ji">Chengyue Ji</name><name sortKey="Jiang, Dongdong" sort="Jiang, Dongdong" uniqKey="Jiang D" first="Dongdong" last="Jiang">Dongdong Jiang</name><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><name sortKey="Luo, Yongjun" sort="Luo, Yongjun" uniqKey="Luo Y" first="Yongjun" last="Luo">Yongjun Luo</name><name sortKey="Rong, Yuluo" sort="Rong, Yuluo" uniqKey="Rong Y" first="Yuluo" last="Rong">Yuluo Rong</name><name sortKey="Wang, Jiaxing" sort="Wang, Jiaxing" uniqKey="Wang J" first="Jiaxing" last="Wang">Jiaxing Wang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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