Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia

Abstract

microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

“…Accordingly, we hypothesized that miR-126-3p promotes carcinogenesis. However, we observed that levels of miR-126-3p in patients with cervical cancer fluctuate (22). We also found variability in the amounts of miR-126-3p in cervical cancer cells themselves (Fig.…”

“…We previously found that miR-126-3p is highly expressed in patients with overt cervical cancer or precursor lesions compared with normal cells (22). Accordingly, we hypothesized that miR-126-3p promotes carcinogenesis.…”

“…MicroRNA-126-3p (miR-126-3p), which has been identified in many types of cancer including lung, breast, gastric, colorectal, glioblastoma, bladder and prostate, may act either as a tumor suppressor by inhibiting oncogenes (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) or as a tumor promoter by inhibiting tumor suppressors (18,19). In cervical cancer, disparate data on the levels of miR-126-3p have been reported, either downregulation in some studies (12,14,20,21) while upregulation in others (15,22), albeit under different experimental conditions. Previous studies have shown that miR-126-3p can target a site in the PI3K subunit p85β (PIK3R2) 3'-UTR, not only in different types of cancer (23)(24)(25)(26) but also in benign diseases (27,28).…”

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia

“…Our results are in accordance with many other studies (Tanaka et al, 2009;Elhamamsy et al, 2017) who reported that mir-92a plasma levels were significantly lower in AML patients and also it was found to be very low in tumor tissues retrieved from patients with gastric cancer (Zhao et al, 2018), However, other studies found that suppression of miR-92a will induce apoptosis and can be considered as a novel method for treatment of Acute Promyelocytic Leukemia (Sharifi et al, 2014). Also, upregulation in miR-92a was observed in colorectal cancer (Elshafei et al, 2017) and cervical cancer (Zhou et al, 2015;Kawai et al, 2018).…”

Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia

“…[6,[8][9][10] Several new biomarkers have been applied for detection of transformed cells aiming to increase the sensitivity and/or specificity of the screening tests and/or in combination with cytology and/or with HPV DNA testing [8,11]. More recently, several groups have demonstrated aberrant expression of microRNAs (miRNAs) in premalignant and malignant cervical lesions, suggesting that this might be used as a more specific biomarker [3,[12][13][14][15][16][17][18][19]. The majority of these works analyzed cervical cancer and/or premalignant lesions, with no surrounding tumor-free tissues coming from the same patient.…”