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


CONCLUSIONS
ZMYM2 may play an important role in sorafenib resistance.
Soon Woo
SW
Nam
Ki Cheol
KC
Park
Hyun Su
HS
Choi
Byoungchun
B
Lee
Sung-Woo
SW
Kim
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015723:Gene Library; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D034741:RNA, Small Interfering; D000077157:Sorafenib; D014157:Transcription Factors / Q000302:isolation & purification / Q000502:physiology*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; D014157:Transcription Factors; C111777:ZMYM2 protein, human; D009536:Niacinamide; D000077157:Sorafenib