MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Dysregulation of glucosaminyl (N-acetyl) transferase 4 (GCNT4) gene and miR-130a-3p gene has been reported in the development of gastric cancer. We elucidated the function of the miR-130a-3p-GCNT4 axis in gastric cancer. R...

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Autores principales:	Wei Hu, Xin Zheng, Jun Liu, Min Zhang, Yan Liang, Ming Song
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	mir-130a-3p gcnt4 gastric cancer proliferation migration Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/f5c2653508ef4c5f96d4e82fcec6933a
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spelling	oai:doaj.org-article:f5c2653508ef4c5f96d4e82fcec6933a2021-11-04T15:51:54ZMicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway2165-59792165-598710.1080/21655979.2021.1995099https://doaj.org/article/f5c2653508ef4c5f96d4e82fcec6933a2021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1995099https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Gastric cancer is the third leading cause of cancer-related deaths worldwide. Dysregulation of glucosaminyl (N-acetyl) transferase 4 (GCNT4) gene and miR-130a-3p gene has been reported in the development of gastric cancer. We elucidated the function of the miR-130a-3p-GCNT4 axis in gastric cancer. Reverse transcription quantitative polymerase chain reaction measured miR-130a-3p and GCNT4 levels in gastric cancer tissues and cells. The interaction between miR-130a-3p and GCNT4 was assessed using luciferase and RNA pull-down assays. Biological roles of miR-130a-3p and GCNT4 were determined using cell proliferation, migration, and invasion assays in gastric cancer cells. In addition, the effect of miR-130a-3p on the tumor growth in vivo was investigated using tumor xenografts assay. Levels of total TGF-β1, phosphorylated SMAD3 (p-SMAD3), and SMAD3 were measured by using western blot. The results showed that miR-130a-3p levels were increased, while GCNT4 levels were reduced in gastric cancer tissues and cell lines. While miR-130a-3p mimics facilitated cellular proliferation, migration, and invasion in vitro, promoted tumor growth in vivo, and activated the TGF-β1/SMAD3 signaling pathway, overexpression of GCNT4 prevented the growth of gastric cancer cells and restrained the activation of the TGF-β1/SMAD3 pathway. Mechanistically, miR-130a-3p suppressed gastric cancer genesis by inhibiting GCNT4 expression and activating the TGF-β1/SMAD3 signaling pathway. Altogether, we proposed that targeting of GCNT4 and activation of the TGF-β1/SMAD3 signaling pathway by miR-130a-3p enhanced the growth of gastric cancer cells. This study provides important strategies for the selection of therapeutic targets for gastric cancer treatment involving miR-130a-3p/GCNT4/ TGF-β1/SMAD3 axis.Wei HuXin ZhengJun LiuMin ZhangYan LiangMing SongTaylor & Francis Grouparticlemir-130a-3pgcnt4gastric cancerproliferationmigrationBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir-130a-3p gcnt4 gastric cancer proliferation migration Biotechnology TP248.13-248.65
spellingShingle	mir-130a-3p gcnt4 gastric cancer proliferation migration Biotechnology TP248.13-248.65 Wei Hu Xin Zheng Jun Liu Min Zhang Yan Liang Ming Song MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
description	Gastric cancer is the third leading cause of cancer-related deaths worldwide. Dysregulation of glucosaminyl (N-acetyl) transferase 4 (GCNT4) gene and miR-130a-3p gene has been reported in the development of gastric cancer. We elucidated the function of the miR-130a-3p-GCNT4 axis in gastric cancer. Reverse transcription quantitative polymerase chain reaction measured miR-130a-3p and GCNT4 levels in gastric cancer tissues and cells. The interaction between miR-130a-3p and GCNT4 was assessed using luciferase and RNA pull-down assays. Biological roles of miR-130a-3p and GCNT4 were determined using cell proliferation, migration, and invasion assays in gastric cancer cells. In addition, the effect of miR-130a-3p on the tumor growth in vivo was investigated using tumor xenografts assay. Levels of total TGF-β1, phosphorylated SMAD3 (p-SMAD3), and SMAD3 were measured by using western blot. The results showed that miR-130a-3p levels were increased, while GCNT4 levels were reduced in gastric cancer tissues and cell lines. While miR-130a-3p mimics facilitated cellular proliferation, migration, and invasion in vitro, promoted tumor growth in vivo, and activated the TGF-β1/SMAD3 signaling pathway, overexpression of GCNT4 prevented the growth of gastric cancer cells and restrained the activation of the TGF-β1/SMAD3 pathway. Mechanistically, miR-130a-3p suppressed gastric cancer genesis by inhibiting GCNT4 expression and activating the TGF-β1/SMAD3 signaling pathway. Altogether, we proposed that targeting of GCNT4 and activation of the TGF-β1/SMAD3 signaling pathway by miR-130a-3p enhanced the growth of gastric cancer cells. This study provides important strategies for the selection of therapeutic targets for gastric cancer treatment involving miR-130a-3p/GCNT4/ TGF-β1/SMAD3 axis.
format	article
author	Wei Hu Xin Zheng Jun Liu Min Zhang Yan Liang Ming Song
author_facet	Wei Hu Xin Zheng Jun Liu Min Zhang Yan Liang Ming Song
author_sort	Wei Hu
title	MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
title_short	MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
title_full	MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
title_fullStr	MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
title_full_unstemmed	MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway
title_sort	microrna mir-130a-3p promotes gastric cancer by targeting glucosaminyl n-acetyl transferase 4 (gcnt4) to regulate the tgf-β1/smad3 pathway
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/f5c2653508ef4c5f96d4e82fcec6933a
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MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway

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