Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer
Identifieur interne : 000B01 ( Main/Exploration ); précédent : 000B00; suivant : 000B02Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer
Auteurs : Shouping Xu [République populaire de Chine] ; Peiyuan Wang [République populaire de Chine] ; Jian Zhang [République populaire de Chine] ; Hao Wu [République populaire de Chine] ; Shiyao Sui [République populaire de Chine] ; Jinfeng Zhang [République populaire de Chine] ; Qin Wang [République populaire de Chine] ; Kun Qiao [République populaire de Chine] ; Weiwei Yang [République populaire de Chine] ; Hongbiao Xu [République populaire de Chine] ; Da Pang [République populaire de Chine]Source :
- Molecular Cancer [ 1476-4598 ] ; 2019.
Abstract
The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer.
Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA
These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of
The online version of this article (10.1186/s12943-019-1017-z) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12943-019-1017-z
PubMed: 30999914
PubMed Central: 6471868
Affiliations:
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institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Peiyuan" sort="Wang, Peiyuan" uniqKey="Wang P" first="Peiyuan" last="Wang">Peiyuan Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Sui, Shiyao" sort="Sui, Shiyao" uniqKey="Sui S" first="Shiyao" last="Sui">Shiyao Sui</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast 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Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Qin" sort="Wang, Qin" uniqKey="Wang Q" first="Qin" last="Wang">Qin Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Qiao, Kun" sort="Qiao, Kun" uniqKey="Qiao K" first="Kun" last="Qiao">Kun Qiao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Weiwei" sort="Yang, Weiwei" uniqKey="Yang W" first="Weiwei" last="Yang">Weiwei Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2204 9268</institution-id><institution-id institution-id-type="GRID">grid.410736.7</institution-id><institution>Department of Pathology,</institution><institution>Harbin Medical University,</institution></institution-wrap>Harbin, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Hongbiao" sort="Xu, Hongbiao" uniqKey="Xu H" first="Hongbiao" last="Xu">Hongbiao Xu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Pang, Da" sort="Pang, Da" uniqKey="Pang D" first="Da" last="Pang">Da Pang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1808 3502</institution-id><institution-id institution-id-type="GRID">grid.412651.5</institution-id><institution>Department of Breast Surgery,</institution><institution>Harbin Medical University Cancer Hospital,</institution></institution-wrap>150 Haping Road, Harbin, 150081 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>150 Haping Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3">Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150086 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular Cancer</title><idno type="eISSN">1476-4598</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer.</p></sec><sec><title>Methods</title><p id="Par2">Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA <italic>EGOT</italic>. Next, the role of <italic>EGOT</italic> in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of <italic>EGOT</italic> enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of <italic>EGOT</italic> expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of <italic>EGOT</italic> in enhancing of paclitaxel sensitivity.</p></sec><sec><title>Results</title><p id="Par3"><italic>EGOT</italic> enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, <italic>EGOT</italic> upregulates ITPR1 levels via formation of a <italic>pre-ITPR1/EGOT</italic> dsRNA that induces <italic>pre-ITPR1</italic> accumulation to increase ITPR1 protein expression <italic>in cis</italic>. On the other hand, <italic>EGOT</italic> recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 <italic>in trans</italic> via two binding motifs in <italic>EGOT</italic> segment 2 (324–645 nucleotides) in exon 1. Moreover, <italic>EGOT</italic> is transcriptionally regulated by stress conditions. Finally, <italic>EGOT</italic> expression enhances paclitaxel sensitivity via assessment of cancer specimens.</p></sec><sec><title>Conclusions</title><p id="Par4">These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of <italic>EGOT</italic> may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1186/s12943-019-1017-z) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author><author><name sortKey="Gaillard, S" uniqKey="Gaillard S">S Gaillard</name></author><author><name sortKey="Phillip, Jm" uniqKey="Phillip J">JM Phillip</name></author><author><name sortKey="Huang, Tc" uniqKey="Huang T">TC Huang</name></author><author><name sortKey="Pinto, Sm" uniqKey="Pinto S">SM Pinto</name></author><author><name sortKey="Tessarollo, Ng" uniqKey="Tessarollo N">NG Tessarollo</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Pandey, 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Bashyal</name></author><author><name sortKey="Mandal, Ss" uniqKey="Mandal S">SS Mandal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghoussaini, M" uniqKey="Ghoussaini M">M Ghoussaini</name></author><author><name sortKey="Fletcher, O" uniqKey="Fletcher O">O Fletcher</name></author><author><name sortKey="Michailidou, K" uniqKey="Michailidou K">K Michailidou</name></author><author><name sortKey="Turnbull, C" uniqKey="Turnbull C">C Turnbull</name></author><author><name sortKey="Schmidt, Mk" uniqKey="Schmidt M">MK Schmidt</name></author><author><name sortKey="Dicks, E" uniqKey="Dicks E">E Dicks</name></author><author><name sortKey="Dennis, J" uniqKey="Dennis J">J Dennis</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Humphreys, Mk" uniqKey="Humphreys M">MK Humphreys</name></author><author><name sortKey="Luccarini, C" uniqKey="Luccarini C">C Luccarini</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xu, Shouping" sort="Xu, Shouping" uniqKey="Xu S" first="Shouping" last="Xu">Shouping Xu</name></noRegion><name sortKey="Pang, Da" sort="Pang, Da" uniqKey="Pang D" first="Da" last="Pang">Da Pang</name><name sortKey="Pang, Da" sort="Pang, Da" uniqKey="Pang D" first="Da" last="Pang">Da Pang</name><name sortKey="Qiao, Kun" sort="Qiao, Kun" uniqKey="Qiao K" first="Kun" last="Qiao">Kun Qiao</name><name sortKey="Sui, Shiyao" sort="Sui, Shiyao" uniqKey="Sui S" first="Shiyao" last="Sui">Shiyao Sui</name><name sortKey="Wang, Peiyuan" sort="Wang, Peiyuan" uniqKey="Wang P" first="Peiyuan" last="Wang">Peiyuan Wang</name><name sortKey="Wang, Qin" sort="Wang, Qin" uniqKey="Wang Q" first="Qin" last="Wang">Qin Wang</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><name sortKey="Xu, Hongbiao" sort="Xu, Hongbiao" uniqKey="Xu H" first="Hongbiao" last="Xu">Hongbiao Xu</name><name sortKey="Yang, Weiwei" sort="Yang, Weiwei" uniqKey="Yang W" first="Weiwei" last="Yang">Weiwei Yang</name><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><name sortKey="Zhang, Jinfeng" sort="Zhang, Jinfeng" uniqKey="Zhang J" first="Jinfeng" last="Zhang">Jinfeng Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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