Upregulation of lncRNA RMRP promotes the activation of cardiac fibroblasts by regulating miR‑613

Abstract

Long non-coding RNAs (lncRNAs) have been reported to serve a key role in a variety of cardiovascular diseases, including in cardiac fibrosis. The present study aimed to investigate the biological role and underlying mechanisms of the induction of cardiac fibroblasts by the lncRNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP). The results demonstrated that RMRP expression was upregulated in the presence of cardiac fibrosis in an abdominal aortic banding-treated rat model. Treatment with angiotensin II increased RMRP expression in cardiac fibroblasts, while the knockdown of RMRP by small-interfering RNA inhibited cardiac fibroblast proliferation, differentiation and collagen accumulation. To further investigate the underlying mechanisms of this interaction, microRNA (miR)-613 was predicted to be a target miR of RMRP and sequence alignment, luciferase activity and MS2 RNA immunoprecipitation were performed to detect the interaction between RMRP and miR-613. The results suggested that RMRP negatively regulated miR-613 in cardiac fibroblasts. Furthermore, miR-613 was indicated to mediate the promoting effect of RMRP on cardiac fibroblast activation. The current study suggested that RMRP promoted cardiac fibroblast activation by acting as a competing endogenous RNA for miR-613. Therefore, RMRP may be a novel target for the prevention or treatment of cardiac fibrosis.

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

“…Steinbusch et al ( 112 ) found associations of RMRP with chondrocyte hypertrophy and determined chondrogenic differentiation, proposing the contribution of RMRP to the modulation of the dynamic balance of ECM degradation and synthesis. Zhang et al ( 113 ) explored the biological role and mechanisms behind CF induction by the lncRNA, RNA component of RMRP. The findings showed that RMRP expression in an abdominal aortic banding–treated rat model was upregulated in the presence of myocardial fibrosis.…”

“…Based on the present study, RMRP increased CF activation with serving as a competing endogenous RNA for miR-613. Thus, RMRP may represent as a novel target to prevent or treat cardiac fibrosis ( 113 ).…”

“…RMRP forms a distinct ribonucleoprotein complex by interaction with the telomerase reverse transcriptase catalytic subunit, which exhibits the activity of RNA-dependent RNA polymerase and makes double-stranded RNAs, which with getting processed can turn into small interfering RNA (siRNA) (106) Based on the present study, RMRP increased CF activation with serving as a competing endogenous RNA for miR-613. Thus, RMRP may represent as a novel target to prevent or treat cardiac fibrosis (113). circRNAs miR-125b induces fibrotic process and upregulation in CFs, indicating numerous binding sites of miR-125b for circ_LAS1L, with inverse association of their expression in those with acute myocardial infarction (AMI) and CFs.…”

Knockdown of long non‐coding RNA RMRP protects cerebral ischemia–reperfusion injury via the microRNA‐613/ATG3 axis and the JAK2/STAT3 pathway

“…For example, RMRP serves as a ceRNA to modulate miR-613 in cardiac fibroblast. 30 RMRP contributes to hypoxia injury initiation via sponging miR-206 to upregulate ATG3 expression. 12 Taken together, RMRP regulates the miR-613/ ATG3 axis in MCAO mice.…”

Age-Related Pathways in Cardiac Regeneration: A Role for lncRNAs?

“…Furthermore, several lncRNAs have been identified as promoters of cardiac fibrosis ( Liang et al, 2018 ; Wang et al, 2018 ; Hao et al, 2019 ; Zhang et al, 2019a ). Aged tissues accumulate signals that promote the epithelial-mesenchymal transition (EMT), inducing the transdifferentiation of epithelial cells to mesenchymal cells, such as fibroblasts, which are the main mediators of fibrosis through the deposition of extracellular matrix.…”