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

Sep 21, 2026

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Cervical cancer (CC) is a common gynecologic malignancy with substantial global mortality. Human papillomavirus (HPV) infection is a major etiological driver, while genetic and epigenetic alterations also shape disease expansion. Circular RNAs (circRNAs), a non-coding RNA subset with covalently closed-loop structures, are abnormally expressed in CC and associate with pathogenesis by regulating key signaling networks. They are proposed as biomarkers and therapeutic targets, and the review summarizes circRNA roles in Wnt/β-catenin, MAPK, and PI3K/Akt/mTOR signaling, angiogenesis, and metastasis, highlighting diagnostic, prognostic, and therapeutic potential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

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Abstract

Introduction

Cervical cancer burden and prevention

HPV infection and histological subtypes

Current treatments and need for new targets

Heydarnia et al. Cell Communication and Signaling (2024) 22:107 [https://doi.org/10.1186/s12964-024-01494-0](https://doi.org/10.1186/s12964-024-01494-0) Cell Communication and Signaling REVIEW Open Access 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 Emad Heydarnia 1†, Zahra Dorostgou2†, Neda Hedayati3†, Vahide Mousavi4, Sheida Yahyazadeh5, Mina Alimohammadi6*, Mobina Gheibi7, Parasta Heidari4*, Somayeh Igder8, Alireza Mafi9,10* and Omid Vakili9,11* 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. Keywords Uterine cervical neoplasms, Human papilloma viruses, Circular RNA, Signal transduction, Diagnosis, Therapeutics †Emad Heydarnia, Zahra Dorostgou and Neda Hedayati contributed equally to this work. *Correspondence: Mina Alimohammadi [mina.alimohammadi11@gmail.com](mina.alimohammadi11@gmail.com); [mina.alimohammadi@sbmu.ac.ir](mina.alimohammadi@sbmu.ac.ir)[ ](mina.alimohammadi@sbmu.ac.ir)Parasta Heidari [parastaheydari@gmail.com](parastaheydari@gmail.com) Alireza Mafi [armafi.m@gmail.com](armafi.m@gmail.com); [armafi@pharm.mui.ac.ir](armafi@pharm.mui.ac.ir) Omid Vakili [o.vakili.isf@gmail.com](o.vakili.isf@gmail.com); [omidvakili@pharm.mui.ac.ir](omidvakili@pharm.mui.ac.ir) Full list of author information is available at the end of the article Introduction Although cervical cancer (CC) is the fourth commonest malignancy among female population, it can be prevented if diagnosed timely, and then cured efficiently [1, 2]. In the context of this malignancy, the uterine cervixlining epithelium is the main site, being affected by cervical tumors, in which the squamocolumnar junctions of both ecto-and endo-cervices are considered as the site of choice for carcinomatous onset and being targeted by the malignant cells [3, 4]. It has been estimated that a significant number of CC cases are developed due to © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/lice

FAQs

How are circular RNAs (circRNAs) linked to cervical cancer development?

Abnormally expressed circRNAs correlate with CC pathogenesis by regulating substantial signaling pathways and influencing processes such as angiogenesis and metastasis.

Which signaling pathways are highlighted in the review as being regulated by circRNAs in HPV-related cervical neoplasms?

The review highlights Wnt/β-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, along with angiogenesis and metastasis-related mechanisms.

Why are circRNAs considered useful for diagnosis and treatment in cervical cancer?

circRNAs can serve as promising biomarkers for diagnosis and prognosis and as therapeutic targets for treatment, because they reflect and regulate disease-relevant molecular pathways.

Sep 21, 2026

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