Function And Mechanism Of MiR-483-3p Downregulating DLC1 Gene In Tumorigenesis Of Colorectal Cancer

Background:The early diagnosis of colorectal cancer (CRC) plays a crucial role in the prognosis and the survival of patients. The previous studies have shown that there has an abnormal expression of some miRNAs between cancer tissues and normal tissues. MiRNAs could not only regulate the expression of tumor suppressor gene either via translational silencing or by inducing mRNA degradation of the targeted genes, but also promote the development and progression of CRC through affecting the activity, invasion, proliferation, migration and drug resistance of cells. The results provide a new vision for clinical applications in cancer diagnosis and clinical therapy.Aims:The aims of study were to detect the expression levels of DLC1 and microRNA-483-3p (miR-483-3p) in the colorectal cancer and adjacent normal tissues, and to investigate the regulatory mechanism of miR-483-3p targeting DLC1 in colorectal cancer development.Methods:The luciferase reporter gene assay was used to validate the downregulation of DLC1 gene by miR-483-3p. Western blotting was used to evaluate the DLC1 levels and quantitative real-time PCR was used to detect the miR-483-3p levels in colorectal cancer and adjacent tissues. The DLC1 protein level was analyzed by Western blot after overexpressing miR-483-3p in HEK293T cells. The proliferation of HCT116 cell regulated by miR-483-3p was measured by CCK8 assay.Results:MiR-483-3p expression levels were significantly higher in colorectal cancer tissues than that in matched normal tissues (p<0.05). DLC1 levels were significantly lower in colorectal cancer tissues than that in matched normal tissues (p<0.05). MiR-483-3p could bind directly on the 3’UTR of DLC1 gene and inhibit the expression of DLC1. Overexpression of miR-483-3p could reduce endogenous DLC1 protein levels in HEK293T cells(p<0.05). In addition, mimic miR-483-3p expression in HCT116 cells could promote their proliferation.Conclusion:MiR-483-3p could promote the proliferation of HCT116 cells by downregulating the expression of target DLC1 gene.