RBMX contributes to hepatocellular carcinoma progression and sorafenib resistance by specifically binding and stabilizing BLACAT1

Hepatocellular carcinoma (HCC) is one of the top five causes of cancer death. The interaction of RNA binding proteins and long no coding RNA play vital role in malignant tumor progression, and even contribute to chemoresistance. RNA binding protein X (RBMX) plays a vital role in binding and stabilizing many proteins. In this study, we have identified RBMX significantly contributes to the tumorigenesis and sorafenib resistance of hepatocellular carcinoma (HCC). We observed that RBMX was highly expressed in both the HCC patient tissues and HCC cell lines. The HCC cell's viability, proliferation, and sorafenib resistance ability were both increased when RBMX was overexpressed. Additional, RBMX also promotes HCC development and chemoresistance in vivo. Further, we found that the autophagy level was increased in HCC cells, which RBMX was up regulated, with sorafenib processing. Interestingly, our study found that long no coding RNA bladder cancer associated transcript 1 (LncBLACAT1) was also raised in HCC. Mechanically, RIP, RNA pull-down and RNA Stability assay proved that RBMX could specially binds BLACAT1's mRNA and matins its expression, which is high degree of consistency with catRAPI database prediction. This mechanism of action is beneficial for cancer cells proliferation, anti-apoptotic, and colony formation with sorafenib treatment. Further, the autophagy level and cancer cell stemness were also improved when RBMX/ BLACAT1 upregulated. Our study indicated that hepatoma cells can improve their proliferation, colony ability and autophagy by RBMX stabilizing BLACAT1 expression then promote HCC development and drug resistance. Hence, RBMX could be considered as novel therapeutic target for HCC treatment strategies.