Identification of Zinc Finger, MYM-type 2 (ZMYM2) as a regulator of sorafenib resistance in hepatocellular carcinoma cell lines

Background and Aim: Hepatocellular carcinoma (HCC) is an aggressive malignancy with a very complex molecular process. There is no successful therapy for advanced HCC at present. Recently, sorafenib has been used as a systemic therapy to improve survival in patients with advanced HCC, but increasing reports of recurrence or non-responsiveness indicate the limitations of sorafenib as a therapeutic agent. Therefore, identification of genes involved in sorafenib resistance is important to effectively treat advanced HCC. Methods: We performed a genomic screening with a short-hairpin RNA library cassette on HCC cell lines to find genes relating resistance to sorafenib. Results: Zinc finger, MYM type 2 (ZMYM2) was sequenced after three successive screens in vitro as a challengeable target. The inhibition of ZMYM2 resulted in sorafenib-resistance in formerly sensitive HCC cell lines. Immunohistochemical comparison of tumor and non-tumor regions showed stronger ZMYM2 staining intensities in non-tumor regions than in tumor regions. Conclusion: ZMYM2 may play an important role in sorafenib resistance.