Research Papers:
Long noncoding RNA RBMY2FP promotes proliferation of male hepatocellular carcinoma by directing DNA methylation and activating RBMY1A1 via DNMT1
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Feng Liu1,2,*, Fu Yang1,*, Xia Wu3,*, Jin-Feng Huang1,*, Ji-Hang Yuan1, Qi-fei Tao4, Gui-hua Jiang3, Jia-sheng Zheng5, Shu-Han Sun1
1Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China
2Reproductive Medical Center, Obstetrics and Gynecology of Navy PLA General Hospital, Beijing 100048, China
3Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
4The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China
5Center of Intervention Oncology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
*These authors have contributed equally to this work
Correspondence to:
Shu-Han Sun, email: [email protected]
Jia-sheng Zheng, email: [email protected]
Keywords: long non-coding RNA, RBMY, DNMT1, DNA methylation, HCC gender disparity
Received: November 25, 2015 Accepted: June 29, 2016 Published: July 30, 2016
ABSTRACT
Sexual dimorphism is a major issue in hepatocellular carcinoma (HCC), with significantly higher incidence in males. We screened male specific Y chromosome transcripts through RNA sequence and discovered a long non-coding RNA RBMY2FP (RNA binding motif protein, Y-linked, family 2, member F pseudogene, lnc-RBMY2FP) that is specifically expressed in about 1/3 male HCC tissues, with no expression in adjacent livers. Positive expression of lnc-RBMY2FP in male HCC is related to poor patient survival. Lnc-RBMY2FP enhances HCC cell growth, proliferation and tumor stemness both in vitro and in vivo. Mechanistically, lnc-RBMY2FP interacts with DNMT1 and hampers its binding onto promoters of RBMY gene family. Thus, maintenance of promoter methylation status is disturbed because of inhibition of DNMT1 activity, leading to increased expression of RBMY1A1 protein and enhanced hepatocarcinogenesis. The finding of lnc-RBMY2FP may partially explain the male preference of HCC and potentially contribute to HCC treatment.