Interactions between Filamin A and MMP-9 Regulate Proliferation and Invasion in Renal Cell Carcinoma

This study aimed to analyze the expression, clinical significance of filamin A (FLNA) in renal cell carcinoma(RCC) and biological effects in a cell line by regulating FLNA expression. Immunohistochemistry and Westernblotting were used to analyze FLNA protein expression in 70 cases of RCC and normal tissues to study therelationship with clinical factors. FLNA lentiviral and empty vectors were transfected into RCC to study theinfluence of up-regulated expression of FLNA. FLNA siRNA was transiently transfected into ACHN kidneycarcinoma cells by a liposome-mediated method and protein was detected by Western blotting. The level ofexpression was found to be significantly lower in RCC than normal tissues (p<0.05). No correlation was notedwith gender, age, tumor size or pathological types (p>0.05), but links with lymph node metastasis, clinic stageand histological grade were noted (p<0.05). Loss of FLNA expression correlated significantly with poor overallsurvival time by Kaplan-Meier analysis (p<0.05). Results for biological function showed that ACHN cellstransfected with FLNA had a lower survival fraction, significant decrease in migration and invasion, higher cellapoptosis, higher percentage of the G0/G1 phases, and lower MMP-9 protein expression compared with ACHNcells untransfected with FLNA (p<0.05). However, renal 786-0 cells transfected with FLNA siRNA had a highersurvival fraction, significant increase in migration and invasion, and higher MMP-9 protein expression compared(p<0.05). In conclusion, FLNA expression was decreased in RCC and correlated significantly with lymph nodemetastasis, clinic stage, histological grade and poor overall survival, suggesting that FLNA may play importantroles as a a tumor suppressor in RCC by promoting degradation of MMP-9.