CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity

Abstract Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogeni...

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Autores principales:	Joshua Miguel C. Danac, Reynaldo L. Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/017c6378fa774ab190e4550c9759c741
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spelling	oai:doaj.org-article:017c6378fa774ab190e4550c9759c7412021-12-02T13:41:43ZCircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity10.1038/s41598-021-88539-32045-2322https://doaj.org/article/017c6378fa774ab190e4550c9759c7412021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88539-3https://doaj.org/toc/2045-2322Abstract Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3′UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.Joshua Miguel C. DanacReynaldo L. GarciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joshua Miguel C. Danac Reynaldo L. Garcia CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
description	Abstract Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3′UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.
format	article
author	Joshua Miguel C. Danac Reynaldo L. Garcia
author_facet	Joshua Miguel C. Danac Reynaldo L. Garcia
author_sort	Joshua Miguel C. Danac
title	CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
title_short	CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
title_full	CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
title_fullStr	CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
title_full_unstemmed	CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
title_sort	circpvt1 attenuates negative regulation of nras by let-7 and drives cancer cells towards oncogenicity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/017c6378fa774ab190e4550c9759c741
work_keys_str_mv	AT joshuamiguelcdanac circpvt1attenuatesnegativeregulationofnrasbylet7anddrivescancercellstowardsoncogenicity AT reynaldolgarcia circpvt1attenuatesnegativeregulationofnrasbylet7anddrivescancercellstowardsoncogenicity
_version_	1718392536458854400

CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity

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