BACKGROUND: DNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa-miR-124 genes in high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) samples with a histological correlation. METHODS: Seventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3-month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in-house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa-miR-124 was performed by multiplex methylation-specific real-time polymerase chain reaction. RESULTS: A positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied. CONCLUSION: The DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi-infection.

• MeSH
• buněčná adhezní molekula 1 genetika   MeSH
• cervix uteri patologie   virologie   MeSH
• cytodiagnostika * MeSH
• dlaždicová intraepiteliální léze cervixu diagnóza   genetika   patologie   virologie   MeSH
• dospělí MeSH
• genotypizační techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• mikro RNA genetika   MeSH
• mladý dospělý MeSH
• nádorové supresorové proteiny genetika   MeSH
• Papanicolaouův test MeSH
• Papillomaviridae patogenita   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• skvamózní intraepiteliální léze diagnóza   genetika   patologie   virologie   MeSH
• vaginální stěr MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cervical cancer is one of the most common malignancies in women. MicroRNAs (miRNAs) are involved in a variety of fundamental cellular processes, including carcinogenesis. The potential utilization of aberrantly expressed miRNAs as novel biomarkers in cervical cancer diagnostics is growing. We investigated miRNA expression profiles during the progression of dysplasia in cervical epithelium to identify aberrantly expressed miRNAs. High-throughput miRNA profiling of high-grade precancerous lesions identified 79 miRNAs showing significant difference in expression values compared to normal cervical epithelium. Ten selected miRNAs were subsequently measured in an independent group of samples to validate them as promising biomarkers of cervical carcinogenesis. MicroRNAs miR-10b-5p, miR-34c-5p, miR-409-3p and miR-411-5p were confirmed as downregulated, while miR-10a-5p, miR-132-3p, miR-141-5p were significantly upregulated in dysplastic cervical tissues. Further investigation revealed an inverse correlation of miR-409-3p with E6 mRNA levels in precancerous cervical lesions. Subsequent in vitro analyses showed a direct involvement of this miRNA in the regulation of E6 oncogene levels, thus confirming a potential tumor suppressor function of miR-409-3p in cervical malignancies. Hence, miR-409-3p may represent a useful early marker and a potential therapeutic target for cervical cancer.

• MeSH
• down regulace MeSH
• lidé MeSH
• lidský papilomavirus 16 genetika   MeSH
• lidský papilomavirus 18 genetika   MeSH
• mikro RNA genetika   MeSH
• nádorové buněčné linie MeSH
• nádory děložního čípku genetika   virologie   MeSH
• onkogenní proteiny virové genetika   MeSH
• regulace genové exprese u nádorů MeSH
• represorové proteiny genetika   MeSH
• skvamózní intraepiteliální léze genetika   virologie   MeSH
• stanovení celkové genové exprese MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH