Profiling of circular RNAs and circTPCN/miR-634/mTOR regulatory pathway in cervical cancer

Abstract

Circular RNAs (circRNAs) are highly stable forms of endogenous non-coding RNA molecules with diverse biological functions. Some of them have been demonstrated to play crucial roles in the initiation or development of cancers through regulation of gene expression. However, the profiles and the roles of circRNAs in tumorigenesis of cervical cancer remain largely unknown. In the current study, we investigated the expression profiles of circRNAs and their potential oncogenic mechanisms in cervical cancer. The expression patterns, obtained using a microarray assay, revealed a total of 192 differentially expressed circRNAs, of which 106 were upregulated and 86 were downregulated, in cervical cancer samples compared with normal cervical samples. The differential expression of circRNAs was validated using quantitative real-time polymerase chain reaction. Two circRNAs (circTPCN and circFAM185A) were confirmed to be significantly upregulated in cervical cancer samples, indicating that they represent potential biomarkers of cervical cancer. The role and the potential molecular mechanism of circTPCN in cervical cancer tumorigenesis were further investigated. Knockdown of circTPCN significantly suppressed proliferation, migration, and invasion and increased apoptosis of cervical cancer cells in vitro. Molecular analysis revealed that circTPCN acted as a sponge of miR-634 to enhance mTOR expression. Thus, the circTPCN/miR-634/mTOR regulatory pathway might be involved in cervical cancer tumorigenesis, and circTPCN is a potential therapeutic target in cervical cancer.