MicroRNA-338-3p suppresses cell proliferation, migration and invasion in human malignant melanoma by targeting MACC1.

ABSTRACT

Malignant melanoma (MM) is the most aggressive form of skin cancer originating from melanocytes with increased proliferative and metastatic ability. Previous studies have revealed that microRNA-338-3p (miR-338-3p) functions as a tumor suppressor in several types of cancer, including cervical cancer, renal cell carcinoma and thyroid cancer. However, the function and mechanism underlying the action of miR-383-3p in MM remain unclear. In the study, aberrant downregulation of miR-338-3p was observed in 60 pairs of MM and adjacent non-tumor tissue using quantitative polymerase chain reaction assay. Decreased miR-383-3p expression was associated with advanced clinical stage (P<0.05) and lymph node metastasis (P<0.001). The overexpression of miR-338-3p in A375 and G361 cells suppressed cell proliferation and migration using MTT, colony formation, wound healing and transwell assays. Mechanistically, MACC1 was identified as a direct target for miR-338-3p using bioinformatics prediction and dual-luciferase assays. Furthermore, MACC1 expression was significantly increased and inversely correlated with the levels of miR-338-3p in MM tissues. More importantly, restoration of MACC1 resulted in reversed the inhibitory effects of miR-338-3p overexpression on MM cells by altering the expression levels of PCNA and epithelial-mesenchymal transition (EMT)-associated proteins. These results suggest that miR-338-3p functions as a novel tumor suppressor, at least in part, via targeting MACC1 and suggest that miR-338-3p may serve as a potential target for treatment of MM patients.