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Sex-dependent interaction of PTGS2 with miR-146a as risk factor for melanoma and the impact of sex hormones in gene expression in skin cells.
- Source :
-
Melanoma research [Melanoma Res] 2024 Aug 01; Vol. 34 (4), pp. 296-306. Date of Electronic Publication: 2024 May 27. - Publication Year :
- 2024
-
Abstract
- Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of sex disparity in melanoma. Post-transcriptional regulation of prostaglandin-endoperoxide synthase (PTGS2) mRNA occurs through a complex interplay of specific trans-acting RNA-binding proteins and microRNAs. MiR-146a is a key player in melanoma, modulating immune responses and tumor microenvironment (TME). Polymorphisms in PTGS2 gene rs20415G<C and miR-146a gene rs2910164G>C have been associated with an increased risk of melanoma. Epistasis between polymorphisms rs20415G<C and rs2910164G>C was investigated by genotyping 453 melanoma patients and 382 control individuals. The effects of testosterone and 17β-estradiol were analyzed in keratinocytes and two melanoma cell lines. The rs2910164GG showed a higher risk in the presence of the genotype rs20417CC in the male population. Testosterone and 17β-estradiol act differently on PTGS2 and miR-146a expression, depending on the cell type. Testosterone augments PTGS2 gene expression in keratinocytes and miR-146a in melanoma cells. While 17β-estradiol only increases miR-146a expression in HaCaT cells. The present study indicates a sex-specific relation between miR-146a and PTGS2 polymorphisms with melanoma cancer risk. Testosterone and 17β-estradiol act differently on the expression of PTGS2 and miR-146a depending on the skin cell type.<br /> (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Subjects :
- Humans
Male
Female
Risk Factors
Middle Aged
Gonadal Steroid Hormones metabolism
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Adult
Sex Factors
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Estradiol metabolism
Aged
Melanoma genetics
Melanoma metabolism
MicroRNAs genetics
MicroRNAs metabolism
Cyclooxygenase 2 metabolism
Cyclooxygenase 2 genetics
Skin Neoplasms genetics
Skin Neoplasms metabolism
Skin Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5636
- Volume :
- 34
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 38934060
- Full Text :
- https://doi.org/10.1097/CMR.0000000000000978