Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure,with noncoding RNAs exerting regulatory influence.However,the molecular function of circular RNAs(circRNAs)in the progression from cardiac hypertrophy to heart failure remains unclear.To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure,we construct a global triple network(microRNA,circRNA,and mRNA)based on the competitive endogenous RNA(ceRNA)theory.We observe that cardiac hypertrophy-related circRNA(circRNA CHRC),within the ceRNA network,is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse cardiomyocytes.Silencing circRNA CHRC increases cross-sectional cell area,atrial natriuretic peptide,andβ-myosin heavy chain levels in primary mouse cardiomyocytes.Further screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro.Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p,while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression.In summary,circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Inter3D:Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription

Topologically associating domain(TAD)reorganization commonly occurs in the cell nucleus and contributes to gene activation and inhibition through the separation or fusion of adjacent TADs.However,functional genes impacted by TAD alteration and the underlying mechanism of TAD reorganization regulating gene transcription remain to be fully elucidated.Here,we first developed a novel approach termed Inter3D to specifically identify genes regulated by TAD reorganization.Our study revealed that the segregation of TADs led to the disruption of intrachromosomal looping at the myosin light chain 12B(MYL12B)locus,via the meticulous reorganization of TADs mediating epigenomic landscapes within tumor cells,thereby exhibiting a significant correlation with the down-regulation of its transcriptional activity.Conversely,the fusion of TADs facilitated intrachromosomal interactions,suggesting a potential association with the activation of cytochrome P450 family 27 subfamily B member 1(CYP27B1).Our study provides comprehensive insight into the capture of TAD rearrangement-mediated gene loci and moves toward understanding the functional role of TAD reorganization in gene transcription.The Inter3D pipeline developed in this study is freely available at https://github.com/bm2-lab/inter3D and https://ngdc.cncb.ac.cn/biocode/tool/BT7399.