Mechanical activation of noncoding-RNA-mediated regulation of disease-associated phenotypes in human cardiomyocytes.

ABSTRACT: How common polymorphisms in noncoding genome regions can regulate cellular function remains largely unknown. Here we show that cardiac fibrosis, mimicked using a hydrogel with controllable stiffness, affects the regulation of the phenotypes of human cardiomyocytes by a portion of the long noncoding RNA ANRIL, the gene of which is located in the disease-associated 9p21 locus. In a physiological environment, cultured cardiomyocytes derived from induced pluripotent stem cells obtained from patients who are homozygous for cardiovascular-risk alleles (R/R cardiomyocytes) or from healthy individuals who are homozygous for nonrisk alleles contracted synchronously, independently of genotype. After hydrogel stiffening to mimic fibrosis, only the R/R cardiomyocytes exhibited asynchrono

SUBMITTER: Kumar A 

PROVIDER: S-EPMC6430136 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature