c-Myc表达正反馈调控促进宫颈癌的恶性进展

Positive feedback regulation of c-Myc expression promotes the malignant progression of cervical cancer

宫颈癌严重威胁着全球妇女的健康。高危型人乳头瘤病毒(human papilloma virus,HPV)感染是宫颈癌的主要危险因素,但并非充分因素。在导致宫颈癌的复杂分子机制中,c-Myc参与的正反馈表达调控作用在放大HPV致癌的效应中占据着重要的位置。HPV癌基因E6和E7诱导c-Myc表达后,c-Myc通过结合基因启动子的E盒序列激活E2F1、eIF4E、GDF-15、CIP2A和某些长链非编码RNA的表达(如CCAT-1和ARAP1-AS1),而这些基因的产物也能够直接或间接反激活c-Myc,从而导致c-Myc表达水平上调。c-Myc与这些因子共同形成了多个正反馈表达调控作用,推动了宫颈癌的恶性转归。如果能阻遏这些调控作用,那么就有可能达到抑制宫颈癌的目的,使患者获益。本文对宫颈癌中存在的c-Myc基因表达正反馈调控作用的研究进展进行了综述,以期为研究宫颈癌的治疗提供新思路。

Cervical cancer is a serious threat to the health of women in the world.High-risk human papillomavirus infection is the main risk factor for cervical cancer,but it is not a sufficient factor.Among the complex molecular mechanisms leading to cervical cancer,c-Myc’s participation in positive feedback expression regulation plays an important role in amplifying the carcinogenic effects of HPV.After being induced to express by the HPV oncogenes E6 and E7,c-Myc activates the expression of E2F1,eIF4E,GDF-15,CIP2A and certain long non-coding RNAs(such as CCAT-1 and ARAP1-AS1)by binding to the E-box sequence of the gene promoter,and the products of these genes can also directly or indirectly deactivate c-Myc,leading to its upregulation.c-Myc and these factors have formed multiple positive feedback expression regulation effects,which promotes the malignant outcome of cervical cancer.If these regulatory effects can be broken,it is possible to achieve the purpose of inhibiting cervical cancer and benefit patients.This paper reviews the research progress of the positive feedback regulation of c-Myc gene expression in cervical cancer to provide new ideas for the study of cervical cancer treatment.