MiR-183-5p promotes renal cell carcinoma metastasis by targeting TET1

Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231184997. doi: 10.1177/03946320231184997.ABSTRACTTen-eleven translocation 1 (TET1) is a member of the DNA demethylase family that regulates the methylation level of the genome. Dysregulation of TET1 in renal cell carcinoma (RCC) may be associated with RCC progression, but the mechanism of TET1 down-regulation in RCC is not yet known. MiR-183-5p is up-regulated in various tumor tissues and acts as an oncogene. We used Transwell and wound healing assays to test cell invasion and migration. To investigate DNA methylation, we used dot blot, which indicates TET1 enzyme activity. We verified the binding of miR-183-5p and TET1 3'-UTR (untranslated region) using dual-luciferase reporter assay. Our study demonstrated, for the first time, that miR-183-5p can directly repress TET1 expression in RCC. We observed a significant decrease in TET1 expression in RCC specimens, as reported in the literature, and a significant decrease in the concentration of 5hmC in RCC. By aligning the microRNA with a database and using the luciferase reporter gene method, we found that miR-183-5p can inhibit luciferase activity by binding to 453-459 bp of TET1 3'-UTR, leading to inhibition of TET1 expression. Furthermore, down-regulation of TET1 inhibited miR-200c expression and promoted RCC cell invasion and migration. Our findings suggest that in RCC, increased expression of miR-183-5p inhibits the expression of TET1, which in turn inhibits the expressio...
Source: International Journal of Immunopathology and Pharmacology - Category: Allergy & Immunology Authors: Source Type: research