MicroRNA-616 promotes the progression of ovarian cancer by targeting TIMP2

Abstract

MicroRNAs (miRNAs), a group of short (~20 nt) non-coding RNAs, play critical roles in the development and progression of ovarian cancer (OC). The role of miR-616, a recently identified cancer-associated miRNA, has never been examined in OC before. The present study demonstrated that the level of miR-616 was increased in OC tissues. A high miR-616 level was associated with poor tumor differentiation and advanced tumor-node-metastasis (TNM) stage. Survival analysis revealed that an elevated level of miR-616 was associated with poor prognosis of OC patients as demonstrated by decreased overall survival (OS) and disease-free survival (DFS). Overexpression of miR-616 promoted the migration, invasion as well as epithelial-mesenchymal transition (EMT) of A2780 cells. Knockdown of miR-616 inhibited these biological functions. Immunohistochemical (IHC) staining revealed that OC tissues with high miR-616 levels exhibited a significantly decreased level of E-cadherin and an increased level of N-cadherin. Furthermore, tissue inhibitor of metalloproteinases 2 (TIMP2) was confirmed to be a direct downstream target of miR-616. Inhibition of TIMP2 expression was required for the promoting effects of miR-616 on the metastasis and EMT of OC cells. Collectively, this study revealed that miR-616 promoted the progression of OC by enhancing cell migration, invasion and EMT.