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Oncol Rep. 2016 Apr;35(4):2297-305. doi: 10.3892/or.2016.4583. Epub 2016 Jan 21.

Methylation and expression of miRNAs in precancerous lesions and cervical cancer with HPV16 infection.

Author information

1
Clinical Research Laboratory, Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39089, México.
2
Direction of Chronic Infections and Cancer, Research Center for Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos 62100, México.
3
Virology and Cancer Epigenetics Laboratory, Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39089, México.
4
Guerrero State Cancer Institute 'Dr Arturo Beltrán Ortega', Acapulco de Juárez, Guerrero 39570, México.
5
Molecular Biomedicine Laboratory, Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39089, México.

Abstract

Abnormal expression and promoter methylation of microRNAs (miRNAs) are common events during cervical carcinogenesis. Worldwide, infection by types 18 and 16 of human papillomaviruses (HPVs) is considered the major risk factor for cervical cancer development. It has been reported that expression of the miRNAs can be deregulated by specific HPV genotypes. In this study we analyzed the promoter methylation of 22 miRNAs and the expression of three miRNAs in 10 non-squamous intraepithelial lesions (Non-SIL) without HPV16 infection, and 7 Non-SIL, 16 low-grade SIL (LSIL) and 16 cervical cancer samples, all with HPV16 infection. The methylation status was determined using Human Cancer miRNA EpiTect Methyl II Signature PCR Array® and the expression of miR-124, miR-218 and miR-193b was determined by qRT-PCR using individual TaqMan assays. Comparisons of groups defined were performed using the Fisher exact test for categorical variables and Mann-Whitney test for continuous variables. A p-value of <0.05 was considered statistically significant. The methylation levels of miR-124-2, miR-218-1, miR-218-2 and miR-34b/c promoters were significantly higher in cervical cancer than in LSIL samples. The methylation levels of miR-193b promoter were significantly lower in cervical cancer than in LSIL samples. The expression of miR-124 and miR-218 was significantly lower in cervical cancer than in LSIL samples. The expression of miR-193b was significantly higher in cervical cancer than in LSIL and Non-SIL samples. Our results suggest that the abnormal promoter methylation and expression of miR-124, miR-218 and miR-193b are common events during cervical carcinogenesis.

PMID:
26797462
DOI:
10.3892/or.2016.4583
[Indexed for MEDLINE]

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