Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis

Haixia Luo; Yuanxing Li; Yueyang Zhao; Jingjing Chang; Xiu Zhang; Binbin Zou; Lifang Gao; Wei Wang

doi:10.3389/fonc.2021.676609

Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis

Front Oncol. 2021 Aug 31:11:676609. doi: 10.3389/fonc.2021.676609. eCollection 2021.

Authors

Haixia Luo¹, Yuanxing Li¹, Yueyang Zhao¹, Jingjing Chang¹, Xiu Zhang¹, Binbin Zou², Lifang Gao³, Wei Wang¹

Affiliations

¹ Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
² Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University, Taiyuan, China.
³ Department of Pathology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Abstract

Circular RNAs (circRNAs) are regulatory molecules that participate in the occurrence, development and progression of tumors. To obtain a complete blueprint of cervical carcinogenesis, we analyzed the temporal transcriptomic landscapes of mRNAs and circRNAs. Microarrays were performed to identify the circRNA and mRNA expression profiles of cervical squamous cell carcinoma (CSCC) and high-grade squamous intraepithelial lesion (HSIL) patients compared with normal controls (NC). Short time-series expression miner (STEM) was utilized to characterize the time-course expression patterns of circRNAs and mRNAs from NC to HSIL and CSCC. A total of 3 circRNA profiles and 3 mRNA profiles with continuous upregulated patterns were identified and selected for further analysis. Furthermore, functional annotation showed that the mRNAs were associated with DNA repair and cell division. The protein-protein interaction (PPI) network analysis revealed that the ten highest-degree genes were considered to be hub genes. Subsequently, a competing endogenous RNA (ceRNA) network analysis and real-time PCR validation indicated that hsa_circ_0001955/hsa-miR-6719-3p/CDK1, hsa_circ_0001955/hsa-miR-1277-5p/NEDD4L and hsa_circ_0003954/hsa-miR-15a-3p/SYCP2 were highly correlated with cervical carcinogenesis. Silencing of hsa_circ_0003954 inhibited SiHa cell proliferation and perturb the cell cycle in vitro. This study provides insight into the molecular events regulating cervical carcinogenesis, identifies functional circRNAs in CSCC, and improves the understanding of the pathogenesis and molecular biomarkers of CSCC and HSIL.

Keywords: bioinformatics; cell cycle; cervical cancer; cervical intraepithelial neoplasia (CIN); circRNAs; high-grade squamous intraepithelial lesions (HSIL).