Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms

Abstract

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/β-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.