The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer—An Update

Abstract

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV’s E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples’ HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV’s protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer.

Human Papilloma Virus Vaccination and Cervical Screening in the Italian Regions: An Overview of the Current State of the Art

“…About 70% of cervical cancers worldwide are caused by HPV types 16 and 18 [5]. Furthermore, cervical cancer is the fourth cause of cancer death in women, with over 600,000 new cases worldwide every year and 342,000 deaths in 2020 [4,6]. It is estimated that during the next 40 years, about 19 million women will die due to cervical cancer without adhesion to screening and preventive treatment [7].…”

NOVAprep-miR-Cervix: New Method for Evaluation of Cervical Dysplasia Severity Based on Analysis of Six miRNAs

“…Metaplastic cells are sensitive to different factors, such as vaginal microbiota, estrogen influence, and viral infection, which synergistically induce epithelial cell proliferation, alteration of paracrine stromal-epithelial interactions, and may eventually promote neoplastic progression [12]. These alterations are associated with specific changes in the cellular miRNA profile [13]. For example, the HPV-16 contributes in the progression of CC by regulating the miR-142/PD-L1 exis [14]; the intercellular adhesive properties of cervical epithelial cells are altered by miR-95 via the suppression of vascular adhesion molecule 1 (VCAM1) [15].…”

Role of MicroRNAs in Cancer Development and Treatment

“…They concluded that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other, possibly due to the discrepancy found among sample types, samples’ HPV status, expression measurements, and methods for analysis. However, miR-34a, miR-9, miR-21, miR-145, and miR-375 were found to be dysregulated across multiple studies, thus highlighting their biomarker properties for cervical pre-cancer detection [ 11 ].…”