miR-377 targets CUL4A and regulates metastatic capability in ovarian cancer

Abstract

The incidence and recurrence rates of ovarian cancer are still high, and once the disease metastasizes, it is nearly always fatal. Cullin 4A (CUL4A) serves a significant role in tumourigenesis and tumour progression; however, the effect and mechanisms underlying CUL4A overexpression are still unknown. The role of microRNAs (miRs) in the regulation of metastatic capability in ovarian cancer cell lines was investigated. The interaction between miR-377 and CUL4A was investigated using bioinformatics analyses and dual-luciferase reporter assays. Furthermore, miR-377 mRNA and protein levels were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively and cell migration and invasion were detected using a Transwell assay. Results revealed that CUL4A expression was negatively associated with miR-377 levels in ovarian cancer tissues and cell lines. Through in silico analysis, the targeting effect of miR-377 on CUL4A was verified. Ectopic expression of miR-377 in SKOV3 cells downregulated the level of CUL4A, and significantly reduced the migratory ability of the cells. miR-377 overexpression led to reduced activity of the Wnt/β-catenin signaling pathway, and regulated the expression of matrix metalloproteinase-2, and 9, and epithelial-mesenchymal transition (EMT)-associated protein. These results suggested that miR-377 is a significant negative regulator of CUL4A that controls cancer cell progression in ovarian cancer cell lines.