"The HPV16 E6, E7/miR-23b-3p/ICAT signaling axis promotes proliferation, migration, invasion and EMT of cervical cancer cells"

作者全名："Hu, Jing; Liao, Deyu; Sun, Zijiu; Ren, Wei; Zhao, Ling; Fang, Yuting; Hu, Kai; Yu, Huomei; Liu, Shiyan; Zhou, Lan; He, Tongchuan; Zhang, Yan"

作者地址："[Hu, Jing; Liao, Deyu; Sun, Zijiu; Fang, Yuting; Hu, Kai; Yu, Huomei; Liu, Shiyan; Zhou, Lan; Zhang, Yan] Chongqing Med Univ, Chinese Minist Educ, Key Lab Diagnost Med Designated, Chongqing 400016, Peoples R China; [Ren, Wei; Zhao, Ling] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [He, Tongchuan] Univ Chicago Med Ctr, Mol Oncol Lab, Chicago, IL 60637 USA"

通信作者："Zhang, Y (通讯作者)，Chongqing Med Univ, Chinese Minist Educ, Key Lab Diagnost Med Designated, Chongqing 400016, Peoples R China."

来源：CARCINOGENESIS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000954266600001

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Cervical cancer (CC) remains one of the most common female malignancies, with higher incidence and mortality rates. more than 99% of CCs are associated with persistent infection with high-risk human papillomavirus. In view of the growing evidence that HPV 16 E6 and E7, two key oncoproteins encoded by HPV 16, regulate the expression of many other multifunctional genes and downstream effectors that contribute to the development of CC. Herein, we undertook a comprehensive effort into how HPV16 E6, E7 oncogenes affect the progression of CC cells. Previous studies have shown that ICAT expression was significantly increased in CC and had a pro-cancer effect. We observed that knockdown of HPV16 E6, E7 expression in SiHa and CasKi cells resulted in significant inhibition of ICAT expression and upregulation of miR-23b-3p expression. Besides, dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p, and negatively modulated by miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of CC cells, such as migration, invasion and EMT. The overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16-positive CC cells. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CaSki cells. Collectively, our findings uncover that HPV16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16-positive CC pathogenesis, which may serve as a promising therapeutic target for HPV16-associated CC. HPV16 E6, E7 oncogenes possess the potential to regulate ICAT via miR-23b-3p and affect the progression of cervical cancer cells, which might provide new insights into the role of HPV16 E6, E7 in the development of cervical carcinoma, and might provide a promising therapeutic strategy against cervical cancer."

基金机构：National Natural Science Foundation of China [81974449]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K202200406]

基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 81974449); and the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K202200406).