RT Journal Article
T1 Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis
A1 Puig-Butille, Joan Anton
A1 Giménez Xavier, Pol
A1 Visconti, Alessia
A1 Nsengimana, Jeremie
A1 Garcia Garcia, Francisco
A1 Tell Marti, Gemma
A1 Escámez Toledano, María José
A1 Newton-Bishop, Julia
A1 Bataile, Veronique
A1 Río Nechaevsky, Marcela del
A1 Dopazo, Joaquin
A1 Falchi, Mario
A1 Puig, Susana
AB The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cutaneous cells. We analysed the gene signature associated with RHC co-cultured melanocytes and keratinocytes by Protein-Protein interaction (PPI) network analysis to identify genes related with non-functional MC1R variants. From two detected networks, we selected 23 nodes as hub genes based on topological parameters. Differential expression of hub genes was then evaluated in healthy skin biopsies from RHC and black hair color (BHC) individuals. We also compared gene expression in melanoma tumors from individuals with RHC versus BHC. Gene expression in normal skin from RHC cutaneous cells showed dysregulation in 8 out of 23 hub genes (CLN3, ATG10, WIPI2, SNX2, GABARAPL2, YWHA, PCNA and GBAS). Hub genes did not differ between melanoma tumors in RHC versus BHC individuals. The study suggests that healthy skin cells from RHC individuals present a constitutive genomic deregulation associated with the red hair phenotype and identify novel genes involved in melanocyte biology.
PB Impact Journals
SN 1949-2553
YR 2017
FD 2017
LK https://hdl.handle.net/10016/38585
UL https://hdl.handle.net/10016/38585
LA eng
NO This work was mainly supported by intramural grants INTRA/07/726.2 and ACCI2014 (U726 and U714) from the Biomedical Network Research on Rare Diseases (CIBERER) of the Instituto de Salud Carlos III, Spain. The research at the Melanoma Unit in Barcelona is partially funded by Spanish Fondo de Investigaciones Sanitarias (PI15/00716 and grants PI15/00956); AGAUR 2014 SGR 603 of the Catalan Government, Spain; European Commission under the 6th Framework Programme, Contract No.LSHC-CT-2006-018702 (GenoMEL) and by the European Commission under the 7th Framework Programme, Diagnoptics; The National Cancer Institute (NCI) of the US National Institute of Health (NIH) (CA83115) and a grant from "Fundació La Marató de TV3, 201331-30", Catalonia, Spain. The Department of Bioengineering UC3M-CIEMAT-IISFJD in Madrid is partially funded from the Spanish Ministerio de Economía y Competitividad (SKINNOVA; SAF2013-43475-R) and (CELLCAM; S2010/BMD-2420) from Comunidad de Madrid. The TwinsUK study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also received support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. MF, VB and AV are supported by BSF grant n. 5044i. The Leeds contribution (tumour gene expressions) was funded by Cancer Research UK Programme grant C588/A19167 and Project GrantC8216/A6129 and NIH Award CA83115.
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RD 1 sept. 2024