In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-16), p. e1010168-
Abstract:
Keloid disorder is a tumour-like disease with invasive growth and a high recurrence rate. Genetic contribution is well expected due to the presence of autosomal dominant inheritance and various genetic mutations in keloid lesions. However, GWAS failed to reveal functional variants in exon regions but single nucleotide polymorphisms in the non-coding regions, suggesting the necessity of innovative genetic investigation. This study employed combined GWAS, RNA-sequence and Hi-C analyses to dissect keloid disorder genetic mechanisms using paired keloid tissues and normal skins. Differentially expressed genes, miRNAs and lncRNAs mined by RNA-sequence were identified to construct a network. From which, 8 significant pathways involved in keloid disorder pathogenesis were enriched and 6 of them were verified. Furthermore, topologically associated domains at susceptible loci were located via the Hi-C database and ten differentially expressed RNAs were identified. Among them, the functions of six molecules for cell proliferation, cell cycle and apoptosis were particularly examined and confirmed by overexpressing and knocking-down assays. This study firstly revealed unknown key biomarkers and pathways in keloid lesions using RNA-sequence and previously reported mutation loci, indicating a feasible approach to reveal the genetic contribution to keloid disorder and possibly to other diseases that are failed by GWAS analysis alone.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010168
DOI:
10.1371/journal.pgen.1010168.g001
DOI:
10.1371/journal.pgen.1010168.g002
DOI:
10.1371/journal.pgen.1010168.g003
DOI:
10.1371/journal.pgen.1010168.g004
DOI:
10.1371/journal.pgen.1010168.g005
DOI:
10.1371/journal.pgen.1010168.g006
DOI:
10.1371/journal.pgen.1010168.s001
DOI:
10.1371/journal.pgen.1010168.s002
DOI:
10.1371/journal.pgen.1010168.s003
DOI:
10.1371/journal.pgen.1010168.s004
DOI:
10.1371/journal.pgen.1010168.s005
DOI:
10.1371/journal.pgen.1010168.s006
DOI:
10.1371/journal.pgen.1010168.s007
DOI:
10.1371/journal.pgen.1010168.s008
DOI:
10.1371/journal.pgen.1010168.s009
DOI:
10.1371/journal.pgen.1010168.s010
DOI:
10.1371/journal.pgen.1010168.s011
DOI:
10.1371/journal.pgen.1010168.s012
DOI:
10.1371/journal.pgen.1010168.s013
DOI:
10.1371/journal.pgen.1010168.s014
DOI:
10.1371/journal.pgen.1010168.s015
DOI:
10.1371/journal.pgen.1010168.s016
DOI:
10.1371/journal.pgen.1010168.s017
DOI:
10.1371/journal.pgen.1010168.s018
DOI:
10.1371/journal.pgen.1010168.r001
DOI:
10.1371/journal.pgen.1010168.r002
DOI:
10.1371/journal.pgen.1010168.r003
DOI:
10.1371/journal.pgen.1010168.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
Permalink