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CircRNA cPWWP2A: an emerging player in diabetes mellitus.

ABSTRACT: Circular RNAs(CircRNAs), a new class of non-coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455-7464, 2019) shown that a novel diabetic retinopathy (DR)-associated CircRNA cPWWP2A, which could act as a competing endogenous RNA interacting with miR-579 to promote the DR-induced retinal vascular dysfunction through up-regulating the expression of Angiopoietin 1, Occludin, and SIRT1. Their findings may provide new insight into the potential use of CircRNA cPWWP2A for the targeted therapy of DR. However, those promising findings may need to be further evaluated detailedly for the following reason. (1) This study doesn't well clarify why the most significantly up-regulated CircRNA mmu _circ_0000254 the fold change of which is 160.581 is excluded,while the cPWWP2A the fold change of which is only 3.487 is chosen. (2) It is difficult to conclude that cPWWP2A competing with miR-579 only by the analysis of colocalization in pericytes.

SUBMITTER: Yan Q

PROVIDER: S-EPMC7511486 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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CircRNA cPWWP2A: an emerging player in diabetes mellitus.

Yan Qijia Q He Xiaoyun X Kuang Gaoyan G Ou Chunlin C

Journal of cell communication and signaling 20200516 3

Circular RNAs(CircRNAs), a new class of non-coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455-7464, 2019) shown that a novel diabetic retinopathy (DR)-associated CircRNA cPWWP2A, which could act as a competing endogenous RNA interacting with m ...[more]

PMID: 32415512

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Project description:ObjectiveLong noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM).MethodsRNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database.ResultsDifferential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network.ConclusionsThis study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network.

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CircRNA cPWWP2A: an emerging player in diabetes mellitus.

Publications

CircRNA cPWWP2A: an emerging player in diabetes mellitus.

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