Microrna-599 targets high-mobility group at-hook 2 to inhibit cell proliferation and invasion in clear cell renal carcinoma

Abstract

Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of clear cell renal cell carcinoma (ccRCC) through their participation in a number of critical biological processes. Therefore, an in-depth investigation into miRNAs and their biological roles within ccRCC may provide useful insights and lead to the identification of novel therapeutic methods for patients with ccRCC. miRNA-599 (miR-599) serves critical roles in different types of human cancer. However, the expression pattern, biological function and molecular mechanism of miR-599 in ccRCC remain unknown. The present study aimed to detect the expression level of miR-599 in ccRCC, examine its effect on ccRCC progression and further explore the possible underlying mechanisms. It was observed that miR-599 was significantly underexpressed in ccRCC tissues and cell lines compared with the control. Functional assays revealed that restored expression of miR-599 restricted the proliferation and invasion of ccRCC cells. Bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that high-mobility group AT-hook 2 (HMGA2) was a direct target of miR-599 in ccRCC. HMGA2 knockdown simulated the suppressive effects caused by miR-599 overexpression in ccRCC. Recovered HMGA2 expression partially rescued the miR-599-mediated inhibition of ccRCC proliferation and invasion. These results suggest that miR-599 may serve tumour suppressive roles in ccRCC by directly targeting HMGA2, indicating that miR-599 may have potential as a treatment for patients with ccRCC.