OncoTargets and Therapy (Aug 2020)
miR-133b Suppresses Invasion and Migration of Gastric Cancer Cells via the COL1A1/TGF-β Axis
Abstract
Yuan Guo, Guochun Lu, Huahui Mao, Shengkun Zhou, Xiangmei Tong, Junfei Wu, Qiang Sun, Hui Xu, Fu Fang Department of General Surgery, First People’s Hospital of Tonglu, Hangzhou 311500, People’s Republic of ChinaCorrespondence: Fu FangDepartment of General Surgery, First People’s Hospital of Tonglu, No. 338 Xuesheng Road, Hangzhou 311500, People’s Republic of ChinaTel +86-15168291988Email [email protected]: The study aimed to explore the mechanism of miR-133b regulating the invasion and migration of gastric cancer (GC) cells via the COL1A1/TGF-β axis.Methods: The miRNA expression profiles of GC downloaded from TCGA database were subjected to differential analysis to determine the target miRNA of interest, and the target genes of the miRNA were predicted by bioinformatics. GSEA was used for gene enrichment analysis. qRT-PCR was carried out to detect gene expression in GC cells. The effect of miR-133b on GC cells was examined by CCK-8, wound healing and Transwell assays. Western blot was conducted to assess the protein expression of EMT-related proteins. The binding relationship between genes was verified by dual-luciferase reporter gene assay.Results: The expression of miR-133b was markedly downregulated in GC tissue, while that of COL1A1 was upregulated. Overexpression of miR-133b decreased the migration and invasion of GC cells, and the EMT process was inhibited as well, while inverse results were observed when miR-133b was silenced. COL1A1 was a target gene of miR-133b and its overexpression had a significant impact on the prognosis of patients. GSEA pathway enrichment results showed that COL1A1 was markedly enriched in the TGF-β signaling pathway. In addition, COL1A1 overexpression induced the activation of the TGF-β signaling pathway to promote proliferation and migration of GC cells, whereas miR-133b overexpression suppressed the signaling pathway. Thus, overexpression of miR-133b and COL1A1 simultaneously would reverse the inhibitory effect of miR-133b on cell invasion and migration.Conclusion: In this study, miR-133b was found to inhibit the invasion and migration of GC cells via the COL1A1/TGF-β axis, which provides a new research direction for the diagnosis and targeted therapy of GC.Keywords: gastric cancer, miR-133b, COL1A1, TGF-β signaling pathway, invasion and migration
