乙肝病毒X蛋白通过DNA甲基化沉默肝癌中miR-338表达

伍刚

乙肝病毒X蛋白通过DNA甲基化沉默肝癌中miR-338表达

伍刚

四川省人民医院肝胆外科

基金项目:

基金：国家自然科学基金资助项目 (81302161); 四川省卫计委科研基金资助项目 (150215);

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出版历程
- 收稿日期: 2017-05-11

HBx Suppresses miR-338 Expression in Hepatoma via DNA Hypermethylation

Wu Gang

Funds:

基金：国家自然科学基金资助项目 (81302161); 四川省卫计委科研基金资助项目 (150215);

摘要

摘要: 目的将HBx相关的DNA甲基化和非编码RNA异常变化联系起来, 研究二者是否存在相互作用.方法利用高通量芯片及qRT-PCR证实HBx在肝癌细胞和组织内下调miR-338表达.通过系列蛋白/mRNA/表达分析, 启动子甲基化检测来研究HBx下调miR-338的机制.结果芯片及qRT-PCR显示HBx在肝癌细胞和组织内下调miR-338的表达.HBx在HepG2肝癌细胞内显著上调DNMT 1和DNMT 3A的表达.HBV阳性肝癌组织中miR-338启动子甲基化程度显著高于癌旁正常组织, 去甲基化处理能挽救肝癌细胞中miR-338表达.结论HBx在体内外显著抑制肝癌中miR-338表达并上调肝癌细胞中DNMT 1和DNMT 3A表达.miR-338启动子过甲基化是其沉默的内在机制.
- HBx /
- miR-338 /
- 甲基化 /
- 肝癌
Abstract: Objective To explore the intereaction between hypermethylation and non-coding RNAs related to Hepatitis B virus X protein (HBx) .hypermethylation.Methods miRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to confirm that HBx suppressed miR-338 expression in HCC cells.Protein, mRNA, miRNA expression analyses and promotor methylation detections were performed to delineate the mechanisms of HBx/HBV associated miR-338 repression in HCC.Results HBx suppressed miR-338 expression in HCC tissues and cells, while upregulating expression of DNMT1 and DNMT3A.The promotor methlation status of miR-338 was significantly higher in HBV+HCC tumors than adjacent tissues, while demethylation treatment could rescue the miR-338 expression in HBx+HCC cells.Conclus ions HBx can downregulate the expression of miR-338, while upregulate DNMT 3 A and DNMT 1 expression.The HBx associated promotor hypermethylation of miR-338 is responsible for its silence.
- HBx /
- miR-338 /
- Methylation /
- Hepatocellular carcinoma

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参考文献(11)

[1]	[1]EL-SERAG HB.Hepatocellular carcinoma[J].N Engl J Med, 2011, 365 (12) :1118-1127.
[2]	[2]KIMC M, KOIKE K, SAITO I, et al.Hbx gene of hepatitis b virus induces liver cancer in transgenic mice[J].Nature, 1991, 351 (6324) :317-320.
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