The role of miR-409-3p in regulation of HPV16/18-E6 mRNA in human cervical high-grade squamous intraepithelial lesions
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30711417
DOI
10.1016/j.antiviral.2019.01.019
PII: S0166-3542(18)30370-X
Knihovny.cz E-resources
- Keywords
- Cervical cancer, E6 mRNA, HPV, HSIL, LSIL, hsa-miR-409-3p, miRNA,
- MeSH
- Down-Regulation MeSH
- Humans MeSH
- Human papillomavirus 16 genetics MeSH
- Human papillomavirus 18 genetics MeSH
- MicroRNAs genetics MeSH
- Cell Line, Tumor MeSH
- Uterine Cervical Neoplasms genetics virology MeSH
- Oncogene Proteins, Viral genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Repressor Proteins genetics MeSH
- Squamous Intraepithelial Lesions genetics virology MeSH
- Gene Expression Profiling MeSH
- Up-Regulation MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- E6 protein, Human papillomavirus type 16 MeSH Browser
- MicroRNAs MeSH
- MIRN409 microRNA, human MeSH Browser
- Oncogene Proteins, Viral MeSH
- Repressor Proteins 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.
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