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Article: Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer

TitleImpaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer
Authors
Issue Date2019
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2019, v. 10 n. 6, article no. 383 How to Cite?
AbstractChemoresistance remains the uppermost disincentive for cancer treatment on account of many genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) are emerging players in promoting cancer initiation and progression. However, the regulation and function in chemoresistance are largely unknown. Herein, we identified ARHGAP5-AS1 as a lncRNA upregulated in chemoresistant gastric cancer cells and its knockdown reversed chemoresistance. Meanwhile, high ARHGAP5-AS1 expression was associated with poor prognosis of gastric cancer patients. Intriguingly, its abundance is affected by autophagy and SQSTM1 is responsible for transporting ARHGAP5-AS1 to autophagosomes. Inhibition of autophagy in chemoresistant cells, thus, resulted in the upregulation of ARHGAP5-AS1. In turn, it activated the transcription of ARHGAP5 in the nucleus by directly interacting with ARHGAP5 promoter. Interestingly, ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of ARHGAP5 mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. In summary, impaired autophagic degradation of lncRNA ARHGAP5-AS1 in chemoresistant cancer cells promoted chemoresistance. It can activate the transcription of ARHGAP5 in the nucleus and stimulate m6A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA in the cytoplasm by recruiting METTL3. Therefore, targeting ARHGAP5-AS1/ARHGAP5 axis might be a promising strategy to overcome chemoresistance in gastric cancer.
Persistent Identifierhttp://hdl.handle.net/10722/301183
ISSN
2023 Impact Factor: 8.1
2023 SCImago Journal Rankings: 2.447
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, L-
dc.contributor.authorZhu, Y-
dc.contributor.authorHan, S-
dc.contributor.authorChen, M-
dc.contributor.authorSong, P-
dc.contributor.authorDai, D-
dc.contributor.authorXu, W-
dc.contributor.authorJiang, T-
dc.contributor.authorFeng, L-
dc.contributor.authorShin, VY-
dc.contributor.authorWang, X-
dc.contributor.authorJin, H-
dc.date.accessioned2021-07-27T08:07:21Z-
dc.date.available2021-07-27T08:07:21Z-
dc.date.issued2019-
dc.identifier.citationCell Death & Disease, 2019, v. 10 n. 6, article no. 383-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/301183-
dc.description.abstractChemoresistance remains the uppermost disincentive for cancer treatment on account of many genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) are emerging players in promoting cancer initiation and progression. However, the regulation and function in chemoresistance are largely unknown. Herein, we identified ARHGAP5-AS1 as a lncRNA upregulated in chemoresistant gastric cancer cells and its knockdown reversed chemoresistance. Meanwhile, high ARHGAP5-AS1 expression was associated with poor prognosis of gastric cancer patients. Intriguingly, its abundance is affected by autophagy and SQSTM1 is responsible for transporting ARHGAP5-AS1 to autophagosomes. Inhibition of autophagy in chemoresistant cells, thus, resulted in the upregulation of ARHGAP5-AS1. In turn, it activated the transcription of ARHGAP5 in the nucleus by directly interacting with ARHGAP5 promoter. Interestingly, ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of ARHGAP5 mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. In summary, impaired autophagic degradation of lncRNA ARHGAP5-AS1 in chemoresistant cancer cells promoted chemoresistance. It can activate the transcription of ARHGAP5 in the nucleus and stimulate m6A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA in the cytoplasm by recruiting METTL3. Therefore, targeting ARHGAP5-AS1/ARHGAP5 axis might be a promising strategy to overcome chemoresistance in gastric cancer.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleImpaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer-
dc.typeArticle-
dc.identifier.emailShin, VY: vyshin@hku.hk-
dc.identifier.authorityShin, VY=rp02000-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-019-1585-2-
dc.identifier.pmid31097692-
dc.identifier.pmcidPMC6522595-
dc.identifier.scopuseid_2-s2.0-85065776426-
dc.identifier.hkuros323788-
dc.identifier.volume10-
dc.identifier.issue6-
dc.identifier.spagearticle no. 383-
dc.identifier.epagearticle no. 383-
dc.identifier.isiWOS:000468673800007-
dc.publisher.placeUnited Kingdom-

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