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Article: APC-activated long non-coding RNA inhibits colorectal carcinoma pathogenesis through reducing exosome production

TitleAPC-activated long non-coding RNA inhibits colorectal carcinoma pathogenesis through reducing exosome production
Authors
Issue Date2019
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 2019, v. 129 n. 2, p. 727-743 How to Cite?
AbstractThe adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development. Long noncoding RNAs (lncRNAs) are invaluable in identifying cancer pathologies and providing therapeutic options for patients with cancer. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening and examined its expression in a large cohort of CRC tissues. A decrease in lncRNA-APC1 expression was positively associated with lymph node and/or distant metastasis, a more advanced clinical stage, as well as a poor prognosis for patients with CRC. Additionally, APC could enhance lncRNA-APC1 expression by suppressing the enrichment of PPARα on the lncRNA-APC1 promoter. Furthermore, enforced lncRNA-APC1 expression was sufficient to inhibit CRC cell growth, metastasis, and tumor angiogenesis by suppressing exosome production through the direct binding of Rab5b mRNA and a reduction of its stability. Importantly, exosomes derived from lncRNA-APC1–silenced CRC cells promoted angiogenesis by activating the MAPK pathway in endothelial cells, and, moreover, exosomal Wnt1 largely enhanced CRC cell proliferation and migration through noncanonicial Wnt signaling. Collectively, lncRNA-APC1 is a critical lncRNA regulated by APC in the pathogenesis of CRC. Our findings suggest that an APC-regulated lncRNA-APC1 program is an exploitable therapeutic approach for the treatment of patients with CRC.
Persistent Identifierhttp://hdl.handle.net/10722/274903
ISSN
2017 Impact Factor: 13.251
2015 SCImago Journal Rankings: 8.764
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWang, FW-
dc.contributor.authorCao, CH-
dc.contributor.authorHan, K-
dc.contributor.authorZhao, YX-
dc.contributor.authorCai, MY-
dc.contributor.authorXiang, ZC-
dc.contributor.authorZhang, JX-
dc.contributor.authorChen, JW-
dc.contributor.authorZhong, LP-
dc.contributor.authorHuang, Y-
dc.contributor.authorZhou, SF-
dc.contributor.authorJin, XH-
dc.contributor.authorGuan, X-
dc.contributor.authorXu, RH-
dc.contributor.authorXie, D-
dc.date.accessioned2019-09-10T02:31:16Z-
dc.date.available2019-09-10T02:31:16Z-
dc.date.issued2019-
dc.identifier.citationJournal of Clinical Investigation, 2019, v. 129 n. 2, p. 727-743-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/274903-
dc.description.abstractThe adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development. Long noncoding RNAs (lncRNAs) are invaluable in identifying cancer pathologies and providing therapeutic options for patients with cancer. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening and examined its expression in a large cohort of CRC tissues. A decrease in lncRNA-APC1 expression was positively associated with lymph node and/or distant metastasis, a more advanced clinical stage, as well as a poor prognosis for patients with CRC. Additionally, APC could enhance lncRNA-APC1 expression by suppressing the enrichment of PPARα on the lncRNA-APC1 promoter. Furthermore, enforced lncRNA-APC1 expression was sufficient to inhibit CRC cell growth, metastasis, and tumor angiogenesis by suppressing exosome production through the direct binding of Rab5b mRNA and a reduction of its stability. Importantly, exosomes derived from lncRNA-APC1–silenced CRC cells promoted angiogenesis by activating the MAPK pathway in endothelial cells, and, moreover, exosomal Wnt1 largely enhanced CRC cell proliferation and migration through noncanonicial Wnt signaling. Collectively, lncRNA-APC1 is a critical lncRNA regulated by APC in the pathogenesis of CRC. Our findings suggest that an APC-regulated lncRNA-APC1 program is an exploitable therapeutic approach for the treatment of patients with CRC.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org-
dc.relation.ispartofJournal of Clinical Investigation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAPC-activated long non-coding RNA inhibits colorectal carcinoma pathogenesis through reducing exosome production-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI122478.-
dc.identifier.pmcidPMC6355227-
dc.identifier.hkuros302592-
dc.identifier.volume129-
dc.identifier.issue2-
dc.identifier.spage727-
dc.identifier.epage743-
dc.publisher.placeUnited States-

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