The profile analysis of circular RNAs in cervical cancer

Abstract

Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.