高危型人乳头瘤病毒感染与宫颈癌中miR-218表达的关系

The relationship between high-risk human papillomavirus infection and the expression of miR-218 in cervical cancer

目的观察高危型人乳头瘤病毒(HPV)感染与宫颈癌中miR-218表达的关系。方法收集2015年6月至2018年12月我院手术切除的宫颈癌组织并检测高危型HPV感染情况和miR-218表达量。培养HPV16阳性的SiHa细胞株并进行分组,阴性对照(NC)组转染NC模拟物、miR-218组转染miR-218模拟物,检测两组细胞凋亡率、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关x蛋白(Bax)、Bcl-2相互作用细胞死亡介导因子(Bim)、含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-9、Caspase-3的mRNA表达量及凋亡通路分子c-Jun氨基末端激酶(JNK)、c-Jun基因(c-Jun)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、哺乳动物雷帕霉素靶蛋白(mTOR)的蛋白表达量。结果高危型HPV阳性的宫颈癌组织中miR-218表达量减少。转染24 h后,miR-218组细胞凋亡率、细胞中Bax、Bim、Caspase-9、Caspase-3的mRNA表达量及JNK、c-Jun的蛋白表达量均明显高于NC组,而细胞中Bcl-2的mRNA表达量及PI3K、AKT、mTOR的蛋白表达量均低于NC组,差异均有统计学意义(均P<0.05)。结论miR-218在高危型HPV感染的宫颈癌组织中表达减少。增加miR-218的表达能够促进HPV感染宫颈癌细胞的凋亡。该调控作用与JNK/c-Jun通路的激活及PI3K/AKT/mTOR通路的抑制有关。

Objective To observe the relationship between high-risk human papillomavirus infection and the expression of miR-218 in cervical cancer. Methods The cervical cancer tissues which were resected in our hospital from June 2015 to December 2018 were collected for detection of high-risk HPV infection and the expression of miR-218. HPV16-positive SiHa cell lines were cultured and grouped. Negative control(NC) group was transfected with NC mimics, and miR-218 group was transfected with miR-218 mimics. The apoptotic rate, mRNA expressions of apoptotic gene B-cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), Bcl-2 interacting mediator of cell death(Bim), cysteinyl aspartate specific proteinase(Caspase)-9 and Caspase-3, as well as the protein expressions of c-Jun N-terminal kinase(JNK), c-Jun gene(c-Jun), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(AKT) and mammalian rapamycin target protein(mTOR). Results The expression of miR-218 in high-risk HPV-positive cervical cancer significantly decreased. 24 hours after transfection, the apoptotic rate, the mRNA expressions of Bax, Bim, Caspase-9 and Caspase-3, and the protein expressions of JNK and c-Jun in miR-218 group were significantly higher than those in the NC group, while the mRNA expression of Bcl-2 and the protein expression of PI3 K, AKT and mTOR were significantly lower than those in the NC group, respectively. Conclusion The expression of miR-218 in high-risk HPV-positive cervical cancer significantly decreased, and miR-218 can promote the apoptosis of cervical cancer cells infected with HPV, which is related to the activation of JNK/c-Jun pathway and the inhibition of PI3 K/AKT/mTOR pathway.