MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway. Issue 2 (20th December 2021)

• Record Type: Journal Article
• Authors: Hu, Wei; Zheng, Xin; Liu, Jun; Zhang, Min; Liang, Yan; Song, Ming
• Is Part Of: Bioengineered. Volume 12:Issue 2(2021)
• Page Start: 11634
• Page End: 11647
• Publication Date: 2021-12-20
• Subjects: Mir-130a-3p -- gcnt4 -- gastric cancer -- proliferation -- migration; Biomedical engineering -- Periodicals; Biotechnology -- Periodicals; Microbiology -- Periodicals; 660.6
• DOI: 10.1080/21655979.2021.1995099
• Languages: English
• ISSNs: 2165-5987

Abstract

ABSTRACT: 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.