Ma Zhuoqun, Zhang Haofeng, Wang Yaqin, Zhao He, Li Yanan, Zhang Jun, Xu Xiaohui
Department of Obstetrics and Gynecology, Beijing Anzhen Hospital Affiliated to Capital Medical University Beijing 100011, China.
Department of Gynecology, University Medical Center Hamburg-Eppendorf (UKE) Hamburg 20246, Germany.
Am J Cancer Res. 2024 Apr 15;14(4):1730-1746. doi: 10.62347/XYCC4213. eCollection 2024.
Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.
越来越多的研究表明，环状RNA（circRNAs）的异常表达与宫颈癌的发生、凋亡及患者预后密切相关。本研究旨在揭示circIL21R在宫颈癌中的促癌作用并探究其相关分子机制。生物信息学分析显示，circIL21R通过miR-1205/PTBP1轴促进宫颈癌进展。circIL21R在肿瘤组织中的表达显著高于相邻正常组织，且circIL21R表达越高表明生存期越短。我们应用MTS实验、EdU实验和Transwell实验表明，circIL21R的过表达促进宫颈癌细胞增殖和侵袭。机制上，circIL21R通过吸附miR-1205促进PTBP1的表达。此外，挽救实验证实，调节miR-1205或PTBP1的表达可逆转circIL21R过表达所致的致瘤效应。另外，circIL21R在体内促进宫颈癌的发生。总之，我们的研究表明，circIL21R在宫颈癌中高表达，并作为miR-1205的竞争性内源RNA上调PTBP1的表达，对宫颈癌的生长、增殖和侵袭等多种恶性生物学过程有突出作用。circIL21R是宫颈癌诊断和治疗的潜在生物标志物。
