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

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.

• Authors: Wei Hu, Xin Zheng, Jun Liu, Min Zhang, Yan Liang, Ming Song
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 2 Pg. 11634-11647 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34696660 (Publication Type: Journal Article)

Chemical References

• MIRN130 microRNA, human
• MicroRNAs
• SMAD3 protein, human
• Smad3 Protein
• TGFB1 protein, human
• Transforming Growth Factor beta1
• N-Acetylglucosaminyltransferases
• beta--1,3-N-acetylglucosaminyltransferase T4

Topics

• Animals
• Base Sequence
• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Disease Progression
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• N-Acetylglucosaminyltransferases (metabolism)
• Neoplasm Invasiveness
• Signal Transduction
• Smad3 Protein (metabolism)
• Stomach Neoplasms (genetics, pathology)
• Transforming Growth Factor beta1 (metabolism)
• Mice