MicroRNA-21 Functions As an Oncogene and Promotes Cell Proliferation and Invasion Via TIMP3 in Renal Cancer

Objective: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence identified microRNAs function as positive or negative regulatory factors in many cancers, but the role of miR-21 in RCC remains unclear.

Patients And Methods: Relative expression levels of miR-21 in human RCC tissue samples and RCC-derived cell lines were measured using quantitative real-time Polymerase Chain Reaction (PCR). Clinical features were collected to further study the relationship between the miR-21 level and clinicopathologic variables. Loss- and gain- of miR-21 experiments were employed to measure the influence of miR-21 in cell proliferation, apoptosis, invasion and migration. Downstream target gene was confirmed by using luciferase and Western blotting assays.

Results: MiR-21 significantly over-expressed in RCC tissues and cell lines than normal groups. Higher miR-21 expression level indicated larger tumor sizes, more lymph metastasis and advanced tumor node metastasis (TNM) stage. Knocking down miR-21 inhibited the cell growth, invasion and migration abilities but promoted the cell apoptosis, while over-expressing miR-21 promoted cell growth and metastasis. Furthermore, TIMP3 was confirmed as a direct target of moR-21 and inhibition of TIMP3 reserved the effect of down-regulating miR-21 in RCC cells.

Conclusions: Our study demonstrated miR-21 was significantly over-expressed and functioned as a tumor oncogene via TIMP3 in RCC, which could provide a potential target for RCC diagnosis and therapy.