MiR-34a and miR-125b Expression in HPV Infection and Cervical Cancer Development.

Joana Ribeiro,Joana Loureiro,Hugo Sousa,Inês Baldaque,Rui Medeiros,Paula Monteiro,Joana Marinho-Dias

doi:10.1155/2015/304584

Joana Ribeiro, Joana Loureiro + Show 5 more

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https://doi.org/10.1155/2015/304584

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Abstract

We aimed to characterize miR-125b and miR-34a expression in 114 women with different cervical lesions: normal epithelium with (n = 20) and without (n = 29) HPV infection; LSIL (n = 28); HSIL (n = 29); and ICC (n = 8). miRNA expression analysis was performed by comparing the distinct groups with the reference group (women with normal epithelium without HPV). For miR-125b, we observed a twofold (2−ΔΔCt = 2.11; P = 0.038) increased expression among women with normal epithelium with HPV infection and a trend of downregulation in different cervical lesions including an 80% reduction (2−ΔΔCt = 0.21; P = 0.004) in ICC. Similarly, miR-34a expression analysis revealed an increased expression (2−ΔΔCt = 1.69; P = 0.049) among women with normal cervix and HPV infection, and despite no significant correlation with cervical lesions, its expression was increased by twofold (2−ΔΔCt = 2.08; P = 0.042) in ICC. Moreover, miR-125b levels were able to predict invasive cancers with 88% sensitivity and 69% specificity. Results showed that while miR-34a expression seems to be correlated with invasive cervical cancer, miR-125b expression is significantly changed within the different cervical lesions and their levels should be further investigated as possible predictive/prognostic biomarkers using a noninvasive approach.

Highlights

Cervical cancer is the third most common cancer among women with approximately 530 000 new cancer cases and 275 100 deaths each year [1, 2]
There are interesting data: firstly, we observed a twofold (2−ΔΔCt = 2.11; P = 0.038) increase in the group of women with normal cytology with human papillomavirus (HPV) infection; despite not being statistically significant, we found a decrease of miR-125b expression for LSIL or HSIL (2−ΔΔCt = 0.75 and 2−ΔΔCt = 0.55, resp.); and, the analysis revealed that miR-125b expression was significantly decreased in women with invasive cervical carcinomas (ICC) (2−ΔΔCt = 0.21; P = 0.004)
MiRNA expression and biological functions are highly influenced by cellular context, probably due to the differential expression of their target messenger RNA (mRNA) [9]

Summary

Introduction

Cervical cancer is the third most common cancer among women with approximately 530 000 new cancer cases and 275 100 deaths each year [1, 2]. The aim of this study was to characterize the expression of two miRNAs (miR-34a and miR-125b) in cytological samples from women with different cervical lesions, including invasive cervical cancers, and evaluate its impact as predictive/prognostic biomarkers of cervical cancer and HPV infection. The study was performed in exfoliated cervical cells collected from randomly selected women (n = 114, median age 40 ± 12.6 years old) attended at the Gynaecological Service from the Portuguese Institute of Oncology of Porto (IPO Porto) during routine clinical observations. The relative quantification of miRNA expression was analyzed using Livak method ( known as 2−ΔΔCt method) In this method, Cts from the target miRNAs (miR-125b and miR-34a) in both test and reference cases were adjusted in relation to the Ct of a normalizer miRNA (miR-23a) resulting in ΔCt. The reference group in this study was women with normal cytology and without HPV infection. Ct: cycle threshold; Sd: standard deviation; VC: variation coefficient; LSIL: low-grade squamous intraepithelial lesions; HSIL: high-grade squamous intraepithelial lesions; ICC: invasive cervical carcinoma

Results

Findings

Discussion