Role of microRNAs as biomarkers of cervical carcinogenesis: a systematic review

Abstract

We performed a systematic review to identify the role of microRNAs (miRNAs) as biomarkers in the progression of cervical precancerous lesions. A comprehensive search of the Cochrane Controlled Register of Trials, PubMed, ScienceDirect, and Embase databases was performed for articles published between January 2010 and June 2020. The following Medical Subject Headings (MeSH) terms were searched: “microRNA” and “cervical” and “lesion.” All study designs that aimed to evaluate the correlation of miRNA expression with different precancerous cervical staging and/or cervical cancer were included, except for case reports and case series. Approximately 82 individual miRNAs were found to be significant in differentiating the stages of cervical carcinogenesis. Among the miRNAs, miR-21 is the most prevalent, and it is consistently upregulated progressively from normal cervical to worsening cervical lesion stages in both cell and serum samples. miR-205 has been shown to have a higher specificity than human papilloma virus testing in predicting the absence of high-grade squamous intraepithelial lesions (HSILs) in exfoliated cell samples. The tumor suppressor miRNAs miR-34, let-7, miR-203 miR-29, and miR-375 were significantly downregulated in low-grade squamous intraepithelial lesions, HSILs, and cervical cancer. We found significant dysregulated miRNAs in cervical carcinogenesis with their dynamic expression changes and ability to detect viral persistency, risk prediction of low-grade lesions (cervical intraepithelial neoplasia [CIN] 2) to high-grade lesions (CIN 3), and progression of CIN 3 to cancer. Their ability to discriminate HSILs from non-dysplastic lesions has potential implications in early diagnosis and reducing overtreatment of otherwise regressive early preinvasive lesions.

The diagnostic accuracy of serum and plasma microRNAs in detection of cervical intraepithelial neoplasia and cervical cancer: A systematic review and meta-analysis

“…Our review found out a number of microRNAs that are either down regulated or up regulated in CIN or cervical cancer. We report many more microRNAs that are down regulated in CIN or cervical cancer compared to a previous systematic review by Nagandla et al ( Nagandla et al, 2021 ) who reported only five microRNAs (miR-34, miR-7, miR-203, miR-29 and miR-375) as down regulated in CIN and cervical cancer. In their systematic review, Pardini et al ( Pardini et al, 2018 ) indicated miR-125b, miR-375, miR-100 and miR-145 as down regulated.…”

“…In their systematic review, Pardini et al ( Pardini et al, 2018 ) indicated miR-125b, miR-375, miR-100 and miR-145 as down regulated. Notable is the up regulation of miR-21 as reported by Nagandla et al ( Nagandla et al, 2021 ) though in exfoliated cervical cells. Also, in a previous systematic review by Pardini et al ( Pardini et al, 2018 ) the notable microRNAs that were indicated as up regulated included miR-9, miR-196a and miR-21.…”

“…We also present the diagnostic accuracy of individual microRNAs or microRNA panels for detection of CIN or cervical cancer compared to healthy controls. Through a literature search, we identified 24 studies, mostly from Chinese and Asian populations, a similar observation from previous reviews ( Nagandla et al, 2021 , Causin, 2021 ), which studied the accuracy of serum or plasma microRNAs in detection of CIN or cervical cancer.…”

“…From our review, we documented that in addition to miR-9, miR-192 and miR-21, miR-205 had a high diagnostic accuracy in detecting CIN or cervical cancer. In a systematic review by Nagandla et al ( Nagandla et al, 2021 ), the authors emphasized a higher sensitivity value of miR-205 for detection of high grade squamous intraepithelial lesions. However, this review reported results of miR-205 expression in exfoliated cervical cells.…”

FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer

“…E7 can also enhance E6-induced telomerase activation by increasing hTERT expression ( 31 ). At present, a large number of dysregulated genes are identified in HPV-CCa ( 32 – 34 ). However, most studies focused on the differentially expressed genes between normal and CCa tissues, and molecular alterations spanning from HPV infection, to CIN and CCa, have rarely been investigated.…”