Involvement of non‑coding RNAs in the pathogenesis of myocardial ischemia/reperfusion injury (Review)

Abstract

Myocardial ischemia/reperfusion injury (MIRI) may cause myocardial stunning, reperfusion arrhythmia, no‑reflow phenomenon and lethal reperfusion injury, which has a significant effect on the prognosis of patients undergoing thrombolytic agent therapy and percutaneous coronary intervention. Increasing evidence suggests that apoptosis, innate inflammation, oxidative stress, calcium overload and autophagy are involved in the pathogenesis of MIRI. Recent advancements in RNA sequencing technologies and genome‑wide analyses led to the finding of small non‑coding RNAs (ncRNAs). ncRNAs modulate cellular processes such as signal transduction, transcription, chromatin remodeling and post‑transcriptional modification. The effects of ncRNAs on cellular biology is more considerable than initially expected, and thus ncRNAs have gained increasing attention and focus in modern medical research. There are several types of ncRNAs, such as microRNAs (miRNAs), long non‑coding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to regulate gene expression at the transcription, post‑transcription and epigenetic levels. Dysregulation of ncRNAs, including miRNAs, lncRNAs and circRNAs, may participate in the molecular mechanisms of MIRI. The present review summarizes the characteristics and biological roles of miRNAs, lncRNAs and circRNAs, with particular emphasis on their role in MIRI, which show the novel complexity of ischemic hearts and may offer valuable insights into the pathogenesis of MIRI.

Keywords: myocardial ischemia/reperfusion injury; microRNA; long non‑coding RNA; circular RNA; therapy.

Figure 1

The biogenesis of miRNA, lncRNA and ciRNA. (a) miRNA genes are transcribed as pri-miRNA by RNA Pol II after which they are mediated by DRCG8 and RNAse III endonuclease Drosha, and pre-miRNA translocates from the nucleus to the cytoplasm mediated by exportin 5. Then, the RNase III endonuclease Dicer interacting with TRBP cleaves the pre-miRNA and mature miRNAs are incorporated into the RISC. (b) LncRNA genes are transcribed mostly by Pol II, and its biogenesis process is similar to miRNA. (c) circRNAs are generated by back-splicing events on maturing pre-mRNA that join together an exon at the upstream 3′ splice site to an exon at the downstream 5′ splice site resulting in a circular product, including exon, intron and exon-intron circRNA. circRNAs that are generated from exons only are mostly found in the cytoplasm, which suggests a role in post-transcriptional gene regulation. pri-miRNA, primary miRNA; Pol II, polymerase II; DRCG8, DiGeorge syndrome criticial region 8; pre-miRNA, precursor miRNA; TRBP, TAR RNA-binding protein; RISC, RNA-induced silencing complex.