E6 and E7 gene silencing results in decreased methylation of tumor suppressor genes and induces phenotype transformation of human cervical carcinoma cell lines.
E6 and E7 gene silencing results in decreased methylation of tumor suppressor genes and induces phenotype transformation of human cervical carcinoma cell lines.
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E6和E7基因沉默导致抑癌基因甲基化减少并诱导人宫颈癌细胞系表型转变。
DOI：
10.18632/oncotarget.4525
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Jiang M
中科院分区：
文献类型：
--
作者：
Li L;Xu C;Long J;Shen D;Zhou W;Zhou Q;Yang J;Jiang M
在 SiHa 和 CaSki 细胞中，E6 和 E7 靶向 shRNA 在转录水平上特异性有效地敲低人乳头瘤病毒 (HPV) 16 E6 和 E7，与表达乱序 shRNA 的对照细胞相比，E6 和 E7 mRNA 水平降低了 80% 以上。与未感染细胞相比，E6和E7抑制导致DNA甲基转移酶mRNA和蛋白表达下调，DNA甲基化减少，抑癌基因mRNA表达水平增加，诱导一定程度的细胞凋亡，并抑制E6和E7 shRNA感染的SiHa和CaSki细胞的增殖。 E6 和 E7 癌基因的抑制导致 DNA 甲基转移酶抑制途径的恢复，并诱导 HPV16 阳性宫颈癌细胞系凋亡。我们的研究结果表明，HPV16 通过影响 DNA 甲基化途径激活宫颈癌的发展的潜在致癌机制是存在的，并且可能作为宫颈癌和其他 HPV 相关癌症的候选治疗策略。
In SiHa and CaSki cells, E6 and E7-targeting shRNA specifically and effectively knocked down human papillomavirus (HPV) 16 E6 and E7 at the transcriptional level, reduced the E6 and E7 mRNA levels by more than 80% compared with control cells that expressed a scrambled-sequence shRNA. E6 and E7 repression resulted in down-regulation of DNA methyltransferase mRNA and protein expression, decreased DNA methylation and increased mRNA expression levels of tumor suppressor genes, induced a certain apoptosis and inhibited proliferation in E6 and E7 shRNA-infected SiHa and CaSki cells compared with the uninfected cells. Repression of E6 and E7 oncogenes resulted in restoration of DNA methyltransferase suppressor pathways and induced apoptosis in HPV16-positive cervical carcinoma cell lines. Our findings suggest that the potential carcinogenic mechanism of HPV16 through influencing DNA methylation pathway to activate the development of cervical cancer exist, and maybe as a candidate therapeutic strategy for cervical and other HPV-associated cancers.