MiR-520f promotes cell aggressiveness by regulating fibroblast growth factor 16 in hepatocellular carcinoma

Abstract

Cancer metastasis is a multistep cellular process, which has be confirmed one of mainly causes of cancer associated-death in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in tumorigenesis function as either tumor suppressor genes or oncogenes. In order to elaborate the critical miRNAs and their targets in HCC, we compared the differential expression of miRNA between HCC tissues and normal tissues. Microarray analysis revealed there were several significantly up-expression miRNAs in HCC, compared to normal solid tissue. Among them, the expression of miR-520f was the most over-expression in HCC cell lines than that in human normal liver cells LO2, as well as up-regulated in HCC than that in the corresponding normal tissues. Moreover, Kaplan Meier-plotter analyses revealed that higher miR-520f levels were negatively correlated with poor overall survival. By applying bioinformatics methods to identify the targeting genes of miRNA, we demonstrated that fibroblast growth factor 16 (FGF16) was the miR-520f-targeted gene. Meanwhile, FGF16 exhibited similar expression patterns to miR-520f in HCC. Forced miR-520f expression accelerated HCC cells proliferation and aggressiveness in vitro and in vivo, whereas down-regulation of miR-520f caused an opposite outcome. Moreover, over-expression of FGF16 was closely related to the metastatic potential of HCC cells. Herein, we also confirmed that ectopic expression of FGF16 in HCC cells promoted proliferation, colony formation, and increased migration, invasion of HCC cells in vitro. Collectively, our results indicated that over-expression of miR-520f and FGF16 was positively associated with aggressive phenotypes and poor survival of patients with HCC, and miR-520f promoted HCC aggressive phenotypes by regulating the expression of FGF16. MiR-520f may be employed as a prognostic factor and therapeutic target for HCC.