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Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases

Abstract

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5′ end and 2′-O-methylation at the 3′ end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

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Abbreviations

ADSCs:

Adipose-derived stem cells

AGO2:

Argonaute 2

ARMI:

Armitage

Aub:

Aubergine

Ccr4-NOT:

Glucose-repressible alcohol dehydrogenase transcriptional effector

DNMT:

DNA methyltransferase

CVDs:

Cardiovascular diseases

Cdk5rap1:

CDK5 regulatory subunit-associated protein 1

CRISPR-Cas:

Clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins

CTEPH:

Chronic thromboembolic pulmonary hypertension

dsRNA:

Double-stranded RNA

ECs:

Endothelial cells

HF:

Heart failure

H3K9me3:

Histone 3 trimethylated on lysine 9

LINE-1:

Long interspersed nuclear elements-1

MI:

Myocardial infarction

MCAF1:

Activating transcription factor 7 interacting protein

MECP2:

Methyl CpG binding protein 2

MM:

Multiple myeloma

MOV10L1:

Mov10-like RISC complex RNA helicase 1

MSCs:

Mesenchymal stem cells

ncRNAs:

Non-coding RNAs

Nbr:

Nibbler

PH:

Pulmonary hypertension

piRNAs:

Piwi-interacting RNAs

piRISCs:

PiRNA-induced silence compounds

PRMT5:

The type II arginine methyltransferasev

qPCR:

Quantitative PCR

RNAi:

RNA interference

RNA-seq:

RNA sequencing

SETDB1:

SET domain-bifurcated histone lysine methyltransferase 1

siRNA:

Small interfering RNA

SUMO:

Small ubiquitin-like modifier

TE:

Transposable element

UDRs:

UORF downstream regions

UHRF1:

Ubiquitin-like, containing PHD and RING finger domains 1

uORFs:

Proximal short open reading frames

WDR77:

WD repeat domain 77

Zuc:

Zucchini

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Acknowledgements

This work was supported by The National Natural Science Foundation of China (Grant No. 81870331, 31701208), The Natural Science Foundation of Shandong Province (Grant No. ZR2017MC067), and The Qingdao municipal science and technology bureau project (Grant No. 18-2-2-65-jch).

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ML, YY, and ZW collected materials and wrote the manuscript. TY and JW provided the idea. KW and TZ are responsible for the schematic diagram within this article. TY, LHHA, and XF helped with the final revision of the article. All authors reviewed the manuscript and approved the final manuscript.

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Correspondence to Tao Yu.

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Li, M., Yang, Y., Wang, Z. et al. Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases. Angiogenesis 24, 19–34 (2021). https://doi.org/10.1007/s10456-020-09750-w

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  • DOI: https://doi.org/10.1007/s10456-020-09750-w

Keywords

  • piRNAs
  • Cvds
  • PIWI proteins
  • ncRNAs
  • Therapy