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LncRNAs and miRs as epigenetic signatures in diabetic cardiac fibrosis: new advances and perspectives

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Abstract

Purpose

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes, which further lead to heartfailure. It is known that diabetes-induced cardiac fibrosis is a key pathogenic factor contributing topathological changes in DCM. However, pathogenetic mechanisms underlying diabetes cardiac fibrosis arestill elusive. Recent studies have indicated that noncoding RNAs (ncRNAs) play a key role in diabetescardiac fibrosis. The increasing complexity of epigenetic regulator poses great challenges to ourconventional conceptions regarding how ncRNAs regulate diabetes cardiac fibrosis.

Methods

We searched PubMed, Web of Science, and Scopus for manuscripts published prior to April 2018 using keywords "Diabetic cardiomyopathy" AND " diabetes cardiac fibrosis " OR " noncoding RNAs " OR " longnoncoding RNAs " OR " microRNAs " OR "epigenetic". Manuscripts were collated, studied and carriedforward for discussion where appropriate.

Results

Based on the view that during diabetic cardiac fibrosis, ncRNAs are able to regulate diabetic cardiac fibrosisby targeting genes involved in epigenetic pathways. Many studies have focused on ncRNAs, an epigeneticregulator deregulating protein-coding genes in diabetic cardiac fibrosis, to identify potential therapeutictargets. Recent advances and new perspectives have found that long noncoding RNAs and microRNAs,exert their own effects on the progression of diabetic cardiac fibrosis.

Conclusion

We firstly examine the growing role of ncRNAs characteristics and ncRNAs-regulated genes involved indiabetic cardiac fibrosis. Then, we provide several possible therapeutic strategies and highlight the potentialof molecular mechanisms in which targeting epigenetic regulators are considered as an effective means of treating diabetic cardiac fibrosis.

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Abbreviations

α-SMA:

α-smooth muscle actin

AGO:

Argonaute

RAAS:

Renin–angiotensin–aldosterone system

LncRNA:

Long noncoding RNA

ECM:

Extracellular matrix

miRs:

MicroRNAs

MI:

Myocardial infarction

ncRNAs:

noncoding RNAs

MMP:

Matrix metalloproteinases

DM:

Diabetes mellitus

TRBP:

TAR RNA binding protein

DCM:

Diabetic cardiomyopathy

EndMT:

Endothelial mesenchymal transition

pre-miR:

precursor miR

TGF-β:

Transforming growth factor beta

UTRs:

untranslated regions

pri-mRNA:

primary mRNA

RNase III:

ribonuclease III

DGCR8:

DiGeorge syndrome critical region gene 8

RISC:

RNA-induced silencing complex

CFs:

cardiac fibroblasts

CTGF:

Connective tissue growth factor

piRNAs:

piwi-interacting RNAs

siRNAs:

short interfering RNAs

HG:

High glucose

IL-6:

Interleukin-6

IL-17:

Interleukin-17

LIPCAR:

Long intergenic noncoding RNA predicting cardiac remodeling

MIAT:

Myocardial infarction-associated transcript

HGF:

Hepatocyte growth factor

STZ:

streptozotocin

DUSP8:

dual specificity phosphatase 8

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Funding

This project was supported by grants from the National Natural Science Foundation of China (81700212 and 81570295) and Natural Science Foundation of Anhui Provincial (1808085MH231) and Natural Science Foundation of Anhui Provincial Education Department (KJ2017A168).

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Authors and Affiliations

  1. School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, 210009, Nanjing, China

    Hui Tao, Zheng-Yu Song & Xuan-Sheng Ding

  2. Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, 230601, Hefei, China

    Hui Tao & Kai-Hu Shi

  3. Department of Pharmacology, The Second Hospital of Anhui Medical University, 230601, Hefei, China

    Jing-Jing Yang

  4. Department of Cardiothoracic Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province, 210028, Nanjing, China

    Kai-Hu Shi

  5. School of Pharmacy, Anhui Medical University, 230032, Hefei, China

    Jun Li

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  1. Hui Tao
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Correspondence to Xuan-Sheng Ding or Kai-Hu Shi.

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The author contributed equally: Zheng-Yu Song.

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Tao, H., Song, ZY., Ding, XS. et al. LncRNAs and miRs as epigenetic signatures in diabetic cardiac fibrosis: new advances and perspectives. Endocrine 62, 281–291 (2018). https://doi.org/10.1007/s12020-018-1688-z

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