miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1

Background: Glioma is the most common cancer in the central nervous system. Previous studies have revealed that the miR-376 family is crucial in tumour development; however, its detailed mechanism in glioma is not clear. Methods: Cellular mRNA or protein levels of miR-376a, SIRT1, VEGF and YAP1 were...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yong-Wen Deng, Yu-Gao Shu, Sheng-Li Sun
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Glioma miR-376a SIRT1 YAP/VEGF signalling Angiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7c62505514084c249ae20254e08ed7c8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7c62505514084c249ae20254e08ed7c8
record_format	dspace
spelling	oai:doaj.org-article:7c62505514084c249ae20254e08ed7c82021-11-22T04:20:14ZmiR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT11936-523310.1016/j.tranon.2021.101270https://doaj.org/article/7c62505514084c249ae20254e08ed7c82022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1936523321002618https://doaj.org/toc/1936-5233Background: Glioma is the most common cancer in the central nervous system. Previous studies have revealed that the miR-376 family is crucial in tumour development; however, its detailed mechanism in glioma is not clear. Methods: Cellular mRNA or protein levels of miR-376a, SIRT1, VEGF and YAP1 were detected via qRT–PCR or Western blotting. We analysed the proliferation, angiogenesis and migration abilities of glioma cell lines using colony formation, tube formation and Transwell assays. A luciferase assay was performed to determine whether miR-376a could recognize SIRT1 mRNA. Xenograft experiments were performed to analyse the tumorigenesis capacity of glioma cell lines in nude mice. The angiogenesis marker CD31 in xenograft tumours was detected via immunohistochemistry (IHC). Results: miR-376a expression was lower in glioma cells than in normal astrocytes. miR-376a mimic inhibited SIRT1, YAP1, and VEGF expression and suppressed the proliferation, migration and angiogenesis abilities of the glioma cell lines LN229 and A172, whereas miR-376a inhibitor exerted the opposite functions. In a luciferase assay, miR-376a inhibited the luciferase activity of WT-SIRT1. SIRT1 overexpression upregulated YAP1 and VEGF in glioma cells and promoted proliferation, migration and angiogenesis. Xenografts with ectopic miR-376a expression exhibited lower volumes and weights and a slower growth curve. Overexpression of miR-376a inhibited YAP1/VEGF signalling and angiogenesis by inhibiting SIRT1 in xenograft tissues. Conclusion: miR-376a directly targets and inhibits SIRT1 in glioma cells. Downregulation of SIRT1 resulted in decreased YAP1 and VEGF signalling, which led to suppression of glioma cell proliferation, migration and angiogenesis.Yong-Wen DengYu-Gao ShuSheng-Li SunElsevierarticleGliomamiR-376aSIRT1YAP/VEGF signallingAngiogenesisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101270- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glioma miR-376a SIRT1 YAP/VEGF signalling Angiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Glioma miR-376a SIRT1 YAP/VEGF signalling Angiogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yong-Wen Deng Yu-Gao Shu Sheng-Li Sun miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
description	Background: Glioma is the most common cancer in the central nervous system. Previous studies have revealed that the miR-376 family is crucial in tumour development; however, its detailed mechanism in glioma is not clear. Methods: Cellular mRNA or protein levels of miR-376a, SIRT1, VEGF and YAP1 were detected via qRT–PCR or Western blotting. We analysed the proliferation, angiogenesis and migration abilities of glioma cell lines using colony formation, tube formation and Transwell assays. A luciferase assay was performed to determine whether miR-376a could recognize SIRT1 mRNA. Xenograft experiments were performed to analyse the tumorigenesis capacity of glioma cell lines in nude mice. The angiogenesis marker CD31 in xenograft tumours was detected via immunohistochemistry (IHC). Results: miR-376a expression was lower in glioma cells than in normal astrocytes. miR-376a mimic inhibited SIRT1, YAP1, and VEGF expression and suppressed the proliferation, migration and angiogenesis abilities of the glioma cell lines LN229 and A172, whereas miR-376a inhibitor exerted the opposite functions. In a luciferase assay, miR-376a inhibited the luciferase activity of WT-SIRT1. SIRT1 overexpression upregulated YAP1 and VEGF in glioma cells and promoted proliferation, migration and angiogenesis. Xenografts with ectopic miR-376a expression exhibited lower volumes and weights and a slower growth curve. Overexpression of miR-376a inhibited YAP1/VEGF signalling and angiogenesis by inhibiting SIRT1 in xenograft tissues. Conclusion: miR-376a directly targets and inhibits SIRT1 in glioma cells. Downregulation of SIRT1 resulted in decreased YAP1 and VEGF signalling, which led to suppression of glioma cell proliferation, migration and angiogenesis.
format	article
author	Yong-Wen Deng Yu-Gao Shu Sheng-Li Sun
author_facet	Yong-Wen Deng Yu-Gao Shu Sheng-Li Sun
author_sort	Yong-Wen Deng
title	miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
title_short	miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
title_full	miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
title_fullStr	miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
title_full_unstemmed	miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1
title_sort	mir-376a inhibits glioma proliferation and angiogenesis by regulating yap1/vegf signalling via targeting of sirt1
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/7c62505514084c249ae20254e08ed7c8
work_keys_str_mv	AT yongwendeng mir376ainhibitsgliomaproliferationandangiogenesisbyregulatingyap1vegfsignallingviatargetingofsirt1 AT yugaoshu mir376ainhibitsgliomaproliferationandangiogenesisbyregulatingyap1vegfsignallingviatargetingofsirt1 AT shenglisun mir376ainhibitsgliomaproliferationandangiogenesisbyregulatingyap1vegfsignallingviatargetingofsirt1
_version_	1718418230926639104

miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1

Ejemplares similares