MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion

Abstract

Purpose. Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods. The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results. The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion. MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.

Silencing of LINC00221 Suppresses Glioblastoma Cell Migration and Invasion through miR-34c-5p/Snai1 and Regulation of Actin and Cytoskeletal Dynamics Proteins

“…Given its consistent presence in multiple predictive bioinformatic databases and the high con dence score indicating its interaction with both upstream LINC00221 and downstream Snai1-3'UTR, miR-34c-5p was chosen as the primary candidate miRNA for further investigation. MiR-34c-5p plays a role in suppressing both cell migration and invasion in both gastric cancer through targeting MAP2K1, and cervical cancer by targeting Notch1 23,24 . In the context of GBM, limited information has been available regarding miR-34c-5p.…”

MicroRNA-34 Family in Cancers: Role, Mechanism, and Therapeutic Potential

“…Furthermore, the long noncoding RNA linc01106 has been identified as a key regulator in GC through its interaction with miR-34a. Linc01106 acts as a sponge for miR-34a, thus sequestering miR-34a and preventing its binding to target mRNAs [68]. Silencing linc01106 has been shown to suppress the malignant behaviors of GC cells by restoring the inhibitory effects of miR-34a on its downstream target gene MYCN.…”

Helicobacter pylori infection accelerates gastric cancer development by acting on the miR-146a-5p/FHL1 axis

“…Recent studies suggest that microRNAs (miRNAs) possess a prominent physiological role in cell growth. 7,8 A growing body of evidence elucidates that H. pylori induce differential expressions of miRNAs in GC.…”