Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its mo...Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration(nmol/mg protein). Status of human IGF-II promoter 3(P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none(0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA(all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II( r s =-0.89, P < 0.001) or liver IGF-II level( r s =-0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.展开更多
基金supported partly by grants from the National Natural Science Foundation(81673241,81702419,81872738,81873915)the Jiangsu Medical Science(BE2016698)&Graduate Innovation(KYCX17_1934)the International S.&T.Coopera-tion Program(2013DFA32150)of China
文摘Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration(nmol/mg protein). Status of human IGF-II promoter 3(P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none(0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA(all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II( r s =-0.89, P < 0.001) or liver IGF-II level( r s =-0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.
