Wang Liming, Shen Hui, Zhu Da, Feng Bei, Yu Lan, Tian Xun, Ren Ci, Gao Chun, Li Xiaomin, Ma Ding, Hu Zheng, Wang Hui
Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Oncotarget. 2018 Jan 9;9(8):7891-7901. doi: 10.18632/oncotarget.24080. eCollection 2018 Jan 30.
Integration of the high risk human papillomavirus (HR-HPV) genome into host chromatin is an important step in cervical carcinogenesis. We identified HR-HPV integration sites within the human genome through detection of integrated papillomavirus sequences-PCR and assessed the role of high mobility group A 2 (HMGA2) in cervical carcinogenesis in clinical samples and cell lines. HPV integration sites were analyzed in 40 cervical cancer samples, while copy number variation and protein expression were assessed in 19 normal cervixes, 49 cervical intraepithelial neoplasia (CIN), and 52 cervical cancer samples. Overall, 25 HR-HPV integrating loci were detected in 24 cervical samples; was the only recurring integration site. Both HPV copy number and HMGA2 protein expression were higher in cervical cancer than CIN samples. Area under the curve (AUC) values for HMGA2 expression and HPV copy number were 0.910 (95% CI: 0.844-0.976) and 0.848 (95% CI: 0.772-0.923), respectively. Expression of and can indicate the cell proliferation and apoptosis. Transfection of HMGA2 siRNA decreased HMGA2 mRNA and protein expression, expression, inhibited cell proliferation, and increased expression and apoptosis in SiHa, CaSki and S12 cervical cancer cells. HMGA2 overexpression had the opposite effects. These results suggest that elevated HMGA2 expression is associated with transformation of CIN into cervical cancer and that HMGA2 might be a useful biomarker for assessing the risk of cervical lesion progression.
高危型人乳头瘤病毒（HR-HPV）基因组整合到宿主染色质中是子宫颈癌发生过程中的重要一步。我们通过检测整合的乳头瘤病毒序列-PCR在人类基因组中鉴定出HR-HPV整合位点，并评估了高迁移率族蛋白A2（HMGA2）在临床样本和细胞系子宫颈癌发生中的作用。在40例宫颈癌样本中分析了HPV整合位点，同时在19例正常子宫颈、49例子宫颈上皮内瘤变（CIN）和52例宫颈癌样本中评估了拷贝数变异和蛋白表达。总体而言，在24例子宫颈样本中检测到25个HR-HPV整合位点；是唯一反复出现的整合位点。宫颈癌中的HPV拷贝数和HMGA2蛋白表达均高于CIN样本。HMGA2表达和HPV拷贝数的曲线下面积（AUC）值分别为0.910（95%CI：0.844-0.976）和0.848（95%CI：0.772-0.923）。和的表达可指示细胞增殖和凋亡。转染HMGA2 siRNA可降低SiHa、CaSki和S12宫颈癌细胞中HMGA2 mRNA和蛋白表达、表达，抑制细胞增殖，并增加表达和凋亡。HMGA2过表达则产生相反的效果。这些结果表明，HMGA2表达升高与CIN转变为宫颈癌有关，并且HMGA2可能是评估宫颈病变进展风险有用的生物标志物。
