Abstract

Background: RNA binding motif protein 3 (RBM3) Is a glycine-rich protein and is considered to be a potential proto-oncogene, but its role and mechanism in Clear Cell Renal Cell Carcinoma (ccRCC) are not clear.

Methods: ccRCC tissues and adjacent tissues from patients and ccRCC cell lines were used to detect the expression of RBM3 and HK2 by RT-PCR and western blot. The RBM3/HK2 activity in ccRCC cell lines was modulated through siRNA and/or inhibitors and the effect on glucose consumption, drug resistance, cell proliferation, invasion, migration and apoptosis were measured by glucose quantification kit, colony formation assay, MTT assay, transwell assay and flow cytometry, respectively. The effect of RBM3 overexpression on ccRCC drug resistance was confirmed in vivo in the nude mice tumor model.

Results: In this study, we found that RBM3 was overexpressed in ccRCC tissues, and overexpression of RBM3 effectively up-regulated glucose consumption and lactic acid production, while RBM3 silencing played the opposite role. In addition, through screening, we found that RBM3 motivated aerobic glycolysis and chemoresistance by promoting the expression of hexokinase 2 (HK2) in renal clear cell carcinoma cells. We also found that HK2 is the key factor of drug resistance induced by RBM3 in ccRCC.

Conclusions: In summary, our results suggest that RBM3 may be a new regulator of glycolysis metabolism and chemotherapy resistance by controlling HK2 in renal clear cell carcinoma cells. This result may help to develop RBM3 as a promising therapeutic target for ccRCC.