The Function And Mechanism Of MiR-193b In Gastric Cancer

MicroRNAs(miRNA) are a class of about 22 nt RNA molecules. MiRNAs have been involved in RNA silencing and post-transcriptional regulation of gene expression and also play important roles in tumorigenesis and tumor progression. Existing evidences reveal that miRNAs not only have pivotal roles in controlling plenty of normal physiological processes, while deregulated microRNAs expression patterns correlate with various diseases, including cancers. Gastric cancer is one of the common malignant diseases. Recently, the function of miRNAs in gastric cancer has attracted wide attention. Cyclin D1 is a protein encoded gene,one member of the greatly conserved cyclin family, characterized by a periodical change in abundance of protein through the cell cycle(G1 phase). This protein interacts with Rb(well-known tumor suppressor protein) and is up-regulated by Rb. Disorder of expression and mutations of cyclin D1 play key role in tumorigenesis by changing the progression of cell cycle. CCND1 has been validated as a direct target of miR-193bPurpose: We aimed to explore the role of miR-193 b in GC carcinogenesis, the aberrant expression of miR-193 b in GC clinical samples, and the detailed mechanism of its functioning.Materials and methods: We investigated the expression of miR-193 b in 50 GC cases compared with the adjacent normal gastric tissues by RT-PCR. We transfected miR-193 b mimics and inhibitors into GC cell lines, HGC-27 and MGC-803, to overexpress and inhibit miR-193 b expression respectively. We also employed CCND1 siRNAs to suppress the expression of CCND1 in GC cells. Cell proliferation assay and cell cycle analysis were preformed to investigate cell growth rates and change of cell cycle. Matastasis and progression of cells were tested by and transwell and wound-healing assays.Results: We found that miR-193 b was significantly reduced in GC tissues. Moreover, lower-level of miR-193 b was also associated with a more aggressive GC phenotype. We further demonstrated that miR-193 b can inhibit the proliferation, migration and invasion of HGC-27 and MGC-803 GC cells. Further mechanism study indicated that CCND1 was a direct target of miR-193 b in GC. Overexpression of miR-193 b inhibited the expression of CCND1, and knock-down of CCND1 inhibited the proliferation of GC cells. MiR-193 b exerted its anti-tumorigenic role in GC cells through targeting CCND1 gene.Conclusion:MicroRNA-193 b inhibits the proliferation, migration and invasion of gastric cancer cells via targeting cyclin D1...