The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication And Growth of Hepatocellular Carcinoma Cells

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx -overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples have also been conducted. Lentivirus -mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx. Cell growth in tetracycline-treated replication-stopping HepAD38 cells was more significantly impaired in ELAVL1 knockdown than those in the control group, indicating that ELAVL1 is involved in proliferation not only by the suppression of HBV replication but also by other factors. Immunohistochemical analyses of 77 paired HCC surgical specimens have demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in nontumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.