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.
Humans
Melanoma
/ genetics
MicroRNAs
/ genetics
Cyclooxygenase 2
/ metabolism
Male
Female
Skin Neoplasms
/ genetics
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
Journal
Melanoma research
ISSN: 1473-5636
Titre abrégé: Melanoma Res
Pays: England
ID NLM: 9109623
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
medline:
27
6
2024
pubmed:
27
6
2024
entrez:
27
6
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38934060
doi: 10.1097/CMR.0000000000000978
pii: 00008390-202408000-00002
doi:
Substances chimiques
MicroRNAs
0
Cyclooxygenase 2
EC 1.14.99.1
MIRN146 microRNA, human
0
PTGS2 protein, human
EC 1.14.99.1
Gonadal Steroid Hormones
0
Estradiol
4TI98Z838E
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
296-306Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
Ribero S, Glass D, Bataille V. Genetic epidemiology of melanoma. Eur J Dermatol 2016; 26:335–339.
Watson M, Holman DM, Maguire-Eisen M. Ultraviolet radiation exposure and its impact on skin cancer risk. Semin Oncol Nurs 2016; 32:241–254.
Pandiani C, Béranger GE, Leclerc J, Ballotti R, Bertolotto C. Focus on cutaneous and uveal melanoma specificities. Genes Dev 2017; 31:724–743.
Qu X, Tang Y, Hua S. Immunological approaches towards cancer and inflammation: a cross talk. Front Immunol 2018; 9:563.
Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms and consequences. Immunity 2019; 51:27–41.
Neagu M, Constantin C, Caruntu C, Dumitru C, Surcel M, Zurac S. Inflammation: a key process in skin tumorigenesis. Oncol Lett 2019; 17:4068–4084.
Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004; 63:901–910.
Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol 2010; 2010:215158.
Xu L, Stevens J, Hilton MB, Seaman S, Conrads TP, Veenstra TD, et al. COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical. Sci Transl Med 2014; 6:242ra84–242ra84.
Pu D, Yin L, Huang L, Qin C, Zhou Y, Wu Q, et al. Cyclooxygenase-2 inhibitor: a potential combination strategy with immunotherapy in cancer. Front Oncol 2021; 11:637504.
Harper KA, Tyson-Capper AJ. Complexity of COX-2 gene regulation. Biochem Soc Trans 2008; 36:543–545.
Ochs MJ, Steinhilber D, Suess B. MicroRNAs – novel therapeutic targets of eicosanoid signalling. Basic Clin Pharmacol Toxicol 2014; 114:92–96.
Young LE, Dixon DA. Posttranscriptional regulation of cyclooxygenase 2 expression in colorectal cancer. Curr Colorectal Cancer Rep 2010; 6:60–67.
Gao F, Zafar MI, Jüttner S, Höcker M, Wiedenmann B. Expression and molecular regulation of the cox2 gene in gastroenteropancreatic neuroendocrine tumors and antiproliferation of nonsteroidal anti-inflammatory drugs (NSAIDs). Med Sci Monit 2018; 24:8125–8140.
Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, et al. Reduced miR-146a increases prostaglandin E₂in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med 2010; 182:1020–1029.
Cornett AL, Lutz CS. Regulation of COX-2 expression by miR-146a in lung cancer cells. RNA 2014; 20:1419–1430.
Vergani E, Dugo M, Cossa M, Frigerio S, Di Guardo L, Gallino G, et al. MiR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators. Cell Communication and Signaling 2020; 18:1–14.
Cebrián A, Gómez Del Pulgar T, Méndez-Vidal MJ, Gonzálvez ML, Lainez N, Castellano D, et al. Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib. Sci Rep 2017; 7:41371.
Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, et al. Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 2002; 22:1631–1636.
Talar-Wojnarowska R, Gasiorowska A, Olakowski M, Lampe P, Smolarz B, Romanowicz-Makowska H, et al. Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis. World J Gastroenterol 2011; 17:4113–4117.
Coskunpinar E, Eraltan IY, Turna A, Agachan B. Cyclooxygenase-2 gene and lung carcinoma risk. Med Oncol 2011; 28:1436–1440.
Zhang XW, Li J, Jiang YX, Chen YX. ‘Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk: a meta-analysis’. World J Gastroenterol 2017; 23:2234–2245.
Gomez-Lira M, Ferronato S, Malerba G, Santinami M, Maurichi A, Sangalli A, et al. Association of promoter polymorphism -765G>C in the PTGS2 gene with malignant melanoma in Italian patients and its correlation to gene expression in dermal fibroblasts. Exp Dermatol 2014; 23:766–768.
Gibney ER, Nolan CM. Epigenetics and gene expression. Heredity (Edinb) 2010; 105:4–13.
Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol 2016; 8:a019505.
Tomankova T, Petrek M, Kriegova E. Involvement of microRNAs in physiological and pathological processes in the lung. Respir Res 2010; 11:1–10.
Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell 2012; 149:515–524.
Syeda ZA, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci 2020; 21:1723.
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 2014; 20:460–469.
Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol 2012; 6:590–610.
Verma M, Bhattacharya S. miRNA in oncogenesis. Trends in Cancer Research and Chemotherapy 2018; 1:1–4.
Otmani K, Lewalle P. Tumor suppressor miRNA in cancer cells and the tumor microenvironment: mechanism of deregulation and clinical implications. Front Oncol 2021; 11:708765.
Latchana N, Ganju A, Howard JH, Carson WE. MicroRNA dysregulation in melanoma’. Surg Oncol 2016; 25:184–189.
Varamo C, Occelli M, Vivenza D, Merlano M, Lo Nigro C. ‘MicroRNAs role as potential biomarkers and key regulators in melanoma’. Genes Chromosomes Cancer 2017; 56:3–10.
Varrone F, Caputo E. The miRNAs role in melanoma and in its resistance to therapy. Int J Mol Sci 2020; 21:878.
Nguyen MHT., et al. miRNA as a modulator of immunotherapy and immune response in melanoma. Biomolecules 2021; 11:1648.
Pu W, Shang Y, Shao Q, Yuan X. miR-146a promotes cell migration and invasion in melanoma by directly targeting SMAD4’. Oncol Lett 2018; 15:7111–7117.
Liu H, Chen M, Wu F, Li F, Yin T, Cheng H, et al. rs2910164 polymorphism confers a decreased risk for pulmonary hypertension by compromising the processing of microRNA-146a. Cell Physiol Biochem 2015; 36:1951–1960.
Nikolić ZZ, Savić Pavićević DL, Vučic NL, Romac SP, Brajušković GN, et al. Association between a Genetic Variant in the HSA-miR-146a gene and cancer risk: an updated meta-analysis. Public Health Genomics 2015; 18:283–298.
Gomez-Lira M, Ferronato S, Orlandi E, Dal Molin A, Malerba G, Frigerio S, et al. Association of microRNA 146a polymorphism rs2910164 and the risk of melanoma in an Italian population. Exp Dermatol 2015; 24:794–795.
Liu Z, Wang D, Hu Y, Zhou G, Zhu C, Yu Q, et al. MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells. J Gastroenterol 2013; 48:86–92.
Wang R, Li M, Zhou S, Zeng D, Xu X, Xu R, et al. Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein expression and lung function in smokers with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015; 10:463–473.
Bellenghi M, Puglisi R, Pontecorvi G, De Feo A, Carè A, Mattia G. Sex and gender disparities in melanoma. Cancers (Basel) 2020; 12:1819–1823.
Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, et al. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol 1997; 11:353–365.
Strouse JJ, Fears TR, Tucker MA, Wayne AS. Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol 2024; 23:4735–4741.
Kemeny MM, Busch E, Stewart AK, Menck HR. Superior survival of young women with malignant melanoma. Am J Surg 1998; 175:437–445.
Natale CA, Li J, Zhang J, Dahal A, Dentchev T, Stanger BZ, et al. Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade. Elife 2018; 7:e31770.
Aguirre-Portoles C, Payne R, Trautz A, Foskett JK, Natale CA, Seykora JT, et al. ZIP9 is a druggable determinant of sex differences in melanoma. Cancer Res 2021; 81:5991–6003.
Pihlajamaa P, Sahu B, Jänne OA. Determinants of receptor- and tissue-specific actions in androgen signaling. Endocr Rev 2015; 36:357–384.
Santana LCL, Spolidorio LC, Pitombo JCP, Basso FG, Guarenghi GG, Prates RC, et al. Testosterone increases fibroblast proliferation in vitro through androgen and estrogen receptor activation. J Int Acad Periodontol 2020; 22:146–155.
Fu R, Liu J, Fan J, Li R, Li D, Yin J, et al. Novel evidence that testosterone promotes cell proliferation and differentiation via G protein-coupled receptors in the rat L6 skeletal muscle myoblast cell line’. J Cell Physiol 2012; 227:98–107.
Rodríguez-Lozano DC, Piña-Medina AG, Hansberg-Pastor V, Bello-Alvarez C, Camacho-Arroyo I. Testosterone promotes glioblastoma cell proliferation, migration, and invasion through androgen receptor activation. Front Endocrinol (Lausanne) 2019; 10:16.
Ahmad M, Weiswald LB, Poulain L, Denoyelle C, Meryet-Figuiere M. Involvement of lncRNAs in cancer cells migration, invasion and metastasis: cytoskeleton and ECM crosstalk. J Exp Clin Cancer Res 2023; 42:1–14.
Wozniak M, Czyz M. Cancers the functional role of long non-coding RNAs in melanoma. 2021; doi: 10.3390/cancers13194848.
Zhao H, Xing G, Wang Y, Luo Z, Liu G, Meng H. Long noncoding RNA HEIH promotes melanoma cell proliferation, migration and invasion via inhibition of miR-200b/a/429. Biosci Rep 2017; 37:20170682.
Pardini B, Calin GA. MicroRNAs and long non-coding RNAs and their hormone-like activities in cancer. Cancers (Basel) 2019; 11:378.
Song HK, Kim SY. The role of sex-specific long non-coding RNAs in cancer prevention and therapy. J Cancer Prev 2021; 26:98–109.
Erfan R, Shaker OG, Khalil MAF, Elsabagh YA, Ahmed AM, Abu-El-Azayem AK, et al. Long non-coding RNA PVT1 and its target miRNA-146a as potential prognostic biomarkers in rheumatoid arthritis patients. Life (Basel) 2021; 11:1382.
Liu HT, Fang L, Cheng YX, Sun Q. LncRNA PVT1 regulates prostate cancer cell growth by inducing the methylation of miR-146a. Cancer Med 2016; 5:3512–3519.
Huang SF, Zhao G, Peng XF, Ye WC. The pathogenic role of long non-coding RNA H19 in atherosclerosis via the miR-146a-5p/ANGPTL4 pathway. Front Cardiovasc Med 2021; 8:770163.
Sangalli A, Orlandi E, Poli A, Maurichi A, Santinami M, Nicolis M, et al. Sex-specific effect of RNASEL rs486907 and miR-146a rs2910164 polymorphisms’ interaction as a susceptibility factor for melanoma skin cancer. Melanoma Res 2017; 27:309–314.
Seo MD, Kang TJ, Lee CH, Lee AY, Noh M. HaCaT keratinocytes and primary epidermal keratinocytes have different transcriptional profiles of Cornified envelope-associated genes to T helper cell cytokines. Biomol Ther (Seoul) 2012; 20:171–176.
Daniotti M, Oggionni M, Ranzani T, Vallacchi V, Campi V, Di Stasi D, et al. BRAF alterations are associated with complex mutational profiles in malignant melanoma. Oncogene 2004; 23:5968–5977.
Watts K, Richardson WJ. Effects of sex and 17 β-estradiol on cardiac fibroblast morphology and signaling activities in vitro. Cells 2021; 10:2564.
Fede C, Pirri C, Fan C, Albertin G, Porzionato A, Macchi V, et al. Sensitivity of the fasciae to sex hormone levels: modulation of collagen-I, collagen-III and fibrillin production. PLoS One 2019; 14:e0223195.
Song W, Khera M. ‘Physiological normal levels of androgen inhibit proliferation of prostate cancer cells in vitro’. Asian J Androl 2014; 16:864–868.
Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. ‘Real-time quantification of microRNAs by stem-loop RT-PCR’. Nucleic Acids Res 2005; 33:e179–e179.
Fochi S, Orlandi E, Ceccuzzi L, Rodolfo M, Vergani E, Turco A, et al. Identification of suitable mRNAs and microRNAs as reference genes for expression analyses in skin cells under sex hormone exposure. Gene 2021; 769:145336.
Maru GB, Hudlikar RR, Kumar G, Gandhi K, Mahimkar MB. Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: from experimental models to clinical trials. World J Biol Chem 2016; 7:88–99.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454:436–444.
Panza E, De Cicco P, Ercolano G, Armogida C, Scognamiglio G, Anniciello AM, et al. Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival. Oncotarget 2016; 7:57077–57085.
Ercolano G, De Cicco P, Rubino V, Terrazzano G, Ruggiero G, Carriero R, et al. Knockdown of PTGS2 by CRISPR/CAS9 system designates a new potential gene target for melanoma treatment. Front Pharmacol 2019; 10:1.
Kang Y-J, Mbonye UR, DeLong CJ, Wada M, Smith WL. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog Lipid Res 2007; 46:108–125.
Mastroianni J, Stickel N, Andrlova H, Hanke K, Melchinger W, Duquesne S, et al. miR-146a controls immune response in the melanoma microenvironment. Cancer Res 2019; 79:183–195.
Permuth-Wey J, Thompson RC, Burton Nabors L, Olson JJ, Browning JE, Madden MH, et al. A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma. J Neurooncol 2011; 105:639–646.
Ha AT, Rahmawati L, You L, Hossain MA, Kim JH, Cho JY. Anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis effects of quercetin 3-O-β-D-glucuronide in human keratinocytes and melanoma cells via activation of NF-κB and AP-1 pathways. Int J Mol Sci 2022; 23:433.
Dao H, Kazin RA. Gender differences in skin: a review of the literature. Gend Med 2007; 4:308–328.
Mitchell DL, Fernandez AA, Garcia R, Paniker L, Lin K, Hanninen A, et al. Acute exposure to ultraviolet-B radiation modulates sex steroid hormones and receptor expression in the skin and may contribute to the sex-bias of melanoma in a fish model. Pigment Cell Melanoma Res 2014; 27:408–417.
Gabriele L, Buoncervello M, Ascione B, Bellenghi M, Matarrese P, Carè A. Monographic section the gender perspective in cancer research and therapy: novel insights and on-going hypotheses. Ann Ist Super Sanità 2016; 52:213–222.
Giacomoni PU, Mammone T, Teri M. Gender-linked differences in human skin. J Dermatol Sci 2009; 55:144–149.
Verdier-Sévrain S, Bonté F, Gilchrest B. Biology of estrogens in skin: implications for skin aging. Exp Dermatol 2006; 15:83–94.
De Giorgi V, Gori A, Grazzini M, Rossari S, Scarfì F, Corciova S, et al. Estrogens, estrogen receptors and melanoma. Expert Rev Anticancer Ther 2011; 11:739–747.
Marzagalli M, Marelli MM, Casati L, Fontana F, Moretti RM, Limonta P. Estrogen receptor β in melanoma: from molecular insights to potential clinical utility. Front Endocrinol (Lausanne) 2016; 7:140.
Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: a review. J Cell Physiol 2019; 234:5683–5699.
Zelenay S, van der Veen AG, Böttcher JP, Snelgrove KJ, Rogers N, Acton SE, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell 2015; 162:1257–1270.
Miao J, Lu X, Hu Y, Piao C, Wu X, Liu X, et al. Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment. Oncotarget 2017; 8:89802–89810.
Haase-Kohn C, Laube M, Donat CK, Belter B, Pietzsch J. CRISPR/Cas9 mediated knockout of cyclooxygenase-2 gene inhibits invasiveness in A2058 melanoma cells. Cells 2022; 11:749.
Liu XM, Li XF, Li JC. MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1. Kaohsiung J Med Sci 2021; 37:286–293.
Meisgen F, Xu Landén N, Wang A, Réthi B, Bouez C, Zuccolo M, et al. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol 2014; 134:1931–1940.
Sun Q, Zhao X, Liu X, Wang Y, Huang J, Jiang B, et al. miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1. Prostate 2014; 74:1613–1621.
Dahiya V, Bagchi G. Non-canonical androgen signaling pathways and implications in prostate cancer. Biochim Biophys Acta Mol Cell Res 2022; 1869:119357.
Dika E, Patrizi A, Lambertini M, Manuelpillai N, Fiorentino M, Altimari A, et al. Estrogen receptors and melanoma: a review. Cells 2019; 8:1463.
Rajabi P, Bagheri M, Hani M. Expression of estrogen receptor alpha in malignant melanoma. Adv Biomed Res 2017; 6:14.
De Giorgi V, Mavilia C, Massi D, Gozzini A, Aragona P, Tanini A, et al. Estrogen receptor expression in cutaneous melanoma a real-time reverse transcriptase-polymerase chain reaction and immunohistochemical study. Arch Dermatol 2009; 145:30–36.