Implication of regulatory networks of long noncoding RNA/circular RNA-miRNA-mRNA in diabetic cardiovascular diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1929-1947
Author(s):  
Wei Xiong ◽  
Mengran Yao ◽  
Yuqiao Yang ◽  
Yan Qu ◽  
Jinqiao Qian

Diabetic cardiovascular diseases (DCVDs) are the most common complications of diabetes mellitus and are considered to be one of the most important threats to global health and an economic burden. Long noncoding RNA (lncRNA), circular RNA (circRNA), and miRNA are a novel group of noncoding RNAs that are involved in the regulation of various pathophysiological processes, including DCVDs. Interestingly, both lncRNA and circRNA can act as competing endogenous RNA of miRNA, thereby regulating the expression of the target mRNA by decoying or sponging the miRNA. In this review, we focus on the mechanistic, pathological and functional roles of lncRNA/circRNA-miRNA-mRNA networks in DCVDs and further discuss the potential implications for early detection, therapeutic intervention and prognostic evaluation.

2018 ◽  
Author(s):  
Benjamin Kleaveland ◽  
Charlie Y. Shi ◽  
Joanna Stefano ◽  
David P. Bartel

SUMMARYNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.HIGHLIGHTSA long noncoding RNA, a circular RNA, and two microRNAs form a regulatory networkThe Cyrano long noncoding RNA directs potent, multiple-turnover destruction of miR-7Unchecked miR-7 prevents accumulation of Cdr1as circular RNA in cytoplasm of neurons miR-7 prevents this accumulation by enhancing the miR-671-directed slicing of Cdr1as


2018 ◽  
Vol 19 (8) ◽  
pp. 2463
Author(s):  
Guoqiang Fan ◽  
Zhe Wang ◽  
Xiaoqiao Zhai ◽  
Yabing Cao

Long noncoding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) are important in the regulation of life activities. However, their function is unclear in Paulownia fortunei. To identify lncRNAs, circRNAs, and miRNA, and investigate their roles in the infection progress of Paulownia witches’ broom (PaWB) disease, we performed RNA sequencing of healthy and infected P. fortunei. A total of 3126 lncRNAs, 1634 circRNAs, and 550 miRNAs were identified. Among them, 229 lncRNAs, 65 circRNAs, and 65 miRNAs were differentially expressed in a significant manner. We constructed a competing endogenous RNA (ceRNA) network, which contains 5 miRNAs, 4 circRNAs, 5 lncRNAs, and 15 mRNAs, all of which were differentially expressed between healthy and infected P. fortunei. This study provides the first catalog of candidate ceRNAs in Paulownia and gives a revealing insight into the molecular mechanism responsible for PaWB.


2021 ◽  
Vol 27 ◽  
Author(s):  
Leiqi Zhu ◽  
Yuanyang Li ◽  
Fangqi Xia ◽  
Mengzhen Xue ◽  
Yaqi Wang ◽  
...  

Background: Increasing academic efforts have been made to explore the correlation of long noncoding RNAs (lncRNAs) with human diseases, particularly metabolic diseases like diabetes mellitus. Taking lncRNA H19 as an example, this review intends to reveal the functions and mechanism of lncRNA H19 in diabetes mellitus and diabetic complications. Methods: The research results associated with lncRNA H19 and diabetes mellitus are collected and summarized on PubMed. Conclusion: LncRNA H19 is a potential instructive marker for the treatment of diabetes mellitus and diabetic complications.


Epigenomics ◽  
2021 ◽  
Author(s):  
Yahong Fu ◽  
Changbin Sun ◽  
Qi Li ◽  
Fengcui Qian ◽  
Chunquan Li ◽  
...  

Aim: To identify differential mRNA and ncRNA expression profiles and competing endogenous RNA-associated regulatory networks during the progression of atherosclerosis (AS). Materials & methods: We systematically analyzed whole-transcriptome sequencing of samples from different stages of AS to evaluate their long noncoding RNA (lncRNA), circular RNA (circRNA), miRNA and mRNA profiles. Results: We constructed three AS-related competing endogenous RNA regulatory networks of differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the circRNAs in the network were enriched in lipid metabolic processes and participated in the PPAR signaling pathway. Furthermore, lncRNAs were related to receptor activity, myofibrils and cardiovascular system development. Conclusion: The current findings further clarified the regulatory mechanisms at different stages of AS and may provide new ideas and targets for AS.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared


Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 65932-65945 ◽  
Author(s):  
Jingjing Li ◽  
Qinghui Zhang ◽  
Xiaoming Fan ◽  
Wenhui Mo ◽  
Weiqi Dai ◽  
...  

2017 ◽  
Vol 88 ◽  
pp. 302-308 ◽  
Author(s):  
Tao Huang ◽  
Hong Wei Liu ◽  
Jia Qi Chen ◽  
Shou Han Wang ◽  
Li Qun Hao ◽  
...  

2021 ◽  
Author(s):  
hafiza sobia ramzan ◽  
Kashif Aziz Ahmad

Background: Osteoarthritis (OA) is a common disease of the joints among old populace until today. The treatment possibilities and roles of miRNA and long non-coding RNA (lncRNA) in therapy of OA has previously been explored. However, the functional roles of Long noncoding RNA KCNQ1OT1 and miRNA let-7a-5p on Osteoarthritis development and progression remains unclear. This study aimed at investigating the influence of KCNQ1OT1 on let-7a-5p in moderation of OA development and advancement. Materials and Methods: RT-qPCR examined expression of KCNQ1OT1and let-7a-5p in cultured human primary chondrocyte cell lines. Cell transfection overexpressed or knocked down the genes and CCK-8 assay measured cell viability in the proliferation biomarkers Ki87 and PCNA. While caspase-8 and caspase-3 activity determined rate of apoptosis. Furthermore, luciferase assay analyzed the luciferase activity and western blotting analysis determined the protein expression of KCNQ1OT1 and let-7a-5p in proliferation and apoptosis biomarkers. Results: The results demonstrated that KCNQ1OT1 is upregulated in OA-mimic cells and promotes the cell viability. KCNQ1OT1 knockdown suppresses cell viability of OA cells. Furthermore KCNQ1OT1 directly binds the 3'-UTR of let-7a-5p to negatively regulate let-7a-5p expression and OA progression. While upregulated let-7a-5p abolishes the proliferation effect of KCNQ1OT1 in OA cells. Conclusion: In summary, our study provides further insights into the underlying molecular mechanisms of KCNQ1OT1 and let-7a-5p suggesting a novel therapeutic approach to OA


RSC Advances ◽  
2019 ◽  
Vol 9 (61) ◽  
pp. 35624-35635 ◽  
Author(s):  
Hui Zhao ◽  
Li Meng ◽  
Chengyang Xu ◽  
Bin Lin ◽  
Xiangming Zheng ◽  
...  

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).


Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Quan Liao

Abstract Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.


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