MicroRNA-195 Inhibits Proliferation And Metastasis In Renal Cell Carcinoma Via Regulating HMGA1

OBJECTIVE: To reveal that miR-195(microRNA-195)acted as a tumor suppressor in RCC(renal cell carcinoma)through inhibition of HMGA1(High Mobility Group Protein A1)expression and provide a theoretical basis for new therapeutic targets.METHODS: First,we analyzed the expression of miR-195 in RCC tissues by TMAS(tissue microarray)and detected the expression of miR-195 in renal cancer cell lines Caki-1 and Caki-2.After miR-195 was overexpressed by using miR-195 mimics in RCC cell lines,the invasion and migration ability and cell cycle of the cells in vitro were examined.The luciferase reporter gene was used to detect whether HMGA1 is a target gene of miR-195.HMGA1 was down-regulated by siRNA(small interfering RNA)and analyzed by EMT(epithelial–mesenchymal transition).Finally,the KaplanMeier method was used to analyze the clinical data of our center and the TCGA(The Cancer Genome Atlas)database to study the relationship between the expression of HMGA1 and the prognosis of RCC patients.RESULTS: The expression of miR-195 was significantly down-regulated in RCC tissues and RCC cell lines.Overexpression of miR-195 reduces the ability of RCC cells to proliferate,cell cycle progression and metastasis in vitro.The luciferase reporter gene confirmed that HMGA1 is a target gene of miR-195.Furthermore,as a target gene for miR-195,up-regulation of HMGA1 re-establishes cellular function of RCC.In clinical specimens,HMGA1 is overexpressed in high-grade RCC tissues,and its expression level is inversely correlated with overall survival compared to its level in normal and low-grade RCC tissues.CONCLUSION: miR-195 plays a key role in the proliferation and metastasis of RCC cells.This study demonstrates that miR-195 and HMGA1 may be potential biomarkers and therapeutic targets for advanced RCC patients...