The roles of circular RNAs in human development and diseases

Lee, Eric Chun Shen; Elhassan, Safa Abdelgadir Mohamed; Lim, Grace Pei Ling; Kok, Weng Hong; Tan, Sze Wei; Leong, Ee Neng; Tan, Sean Hong; Chan, Elaine Wan Ling; Bhattamisra, Subrat Kumar; Rajendran, Ramkumar; Candasamy, Mayuren

doi:10.1016/j.biopha.2018.12.052

Cited by 88 publications

(75 citation statements)

References 104 publications

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“…CircRNAs, a new type of ncRNAs formed by special loop splicing, are thought to be potential diagnostic biomarkers and therapeutic targets because they are more stable and conserved than other RNAs (Lee et al, 2019). However, very few studies have focused on the role of circRNAs in IDD development.…”

Section: Discussionmentioning

confidence: 99%

Integrating multiple microarray dataset analysis and machine learning methods to reveal the key genes and regulatory mechanisms underlying human intervertebral disc degeneration

Chang

Yang

You

et al. 2020

PeerJ

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Intervertebral disc degeneration (IDD), a major cause of lower back pain, has multiple contributing factors including genetics, environment, age, and loading history. Bioinformatics analysis has been extensively used to identify diagnostic biomarkers and therapeutic targets for IDD diagnosis and treatment. However, multiple microarray dataset analysis and machine learning methods have not been integrated. In this study, we downloaded the mRNA, microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) expression profiles (GSE34095, GSE15227, GSE63492 GSE116726, GSE56081 and GSE67566) associated with IDD from the GEO database. Using differential expression analysis and recursive feature elimination, we extracted four optimal feature genes. We then used the support vector machine (SVM) to make a classification model with the four optimal feature genes. The ROC curve was used to evaluate the model’s performance, and the expression profiles (GSE63492, GSE116726, GSE56081, and GSE67566) were used to construct a competitive endogenous RNA (ceRNA) regulatory network and explore the underlying mechanisms of the feature genes. We found that three miRNAs (hsa-miR-4728-5p, hsa-miR-5196-5p, and hsa-miR-185-5p) and three circRNAs (hsa_circRNA_100723, hsa_circRNA_104471, and hsa_circRNA_100750) were important regulators with more interactions than the other RNAs across the whole network. The expression level analysis of the three datasets revealed that BCAS4 and SCRG1 were key genes involved in IDD development. Ultimately, our study proposes a novel approach to determining reliable and effective targets in IDD diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Integrating multiple microarray dataset analysis and machine learning methods to reveal the key genes and regulatory mechanisms underlying human intervertebral disc degeneration

Chang

Yang

You

et al. 2020

PeerJ

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“…It causes most of the deaths worldwide [35]. According to recent studies, a number of circRNAs may play a significant role during development of CVD or pathological conditions such as cardiac hypertrophy, coronary artery disease, atherosclerotic vascular disease, cardiomyopathy, cardiac fibrosis, heart failure (HF), ischemia, and myocardial infarction (MI) [36][37][38]. However, in development of heart disease, the regulatory mechanisms and functional importance of several circRNAs are not clear [38].…”

Section: Circrnas In Cardiovascular Diseasesmentioning

confidence: 99%

Circular RNAs and Its Biological Functions in Health and Disease

Sağlam¹,

Alp²,

Onen³

2020

Gene Expression and Phenotypic Traits

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Circular RNAs (circRNAs) belong to the family of long noncoding RNAs (lncRNA) that, unlike linear RNAs, are characterized by a covalently closed circular RNA structure lacking 5 0 cap and 3 0 poly-adenylated tails. circRNAs have a role in epigenetic regulation of downstream targets. circRNAs play a crucial role in regulating gene and protein expressions by acting as a microRNA (miRNA) sponge and RNA binding protein (RBP) sponge and interact with proteins to affect cell behavior. circRNA expression profiles differ between physiological and pathological states. Moreover, the expression patterns of circRNAs exhibit differences in a tissue-specific manner. Although investigations on circRNAs have been exploding nowadays, yet only a limited number of circRNAs are identified. Furthermore, further researches are needed to shed light on their functions and targets. Therefore, circRNAs are becoming vital as potential biomarkers that may be used for the diagnosis and treatment of diseases. In this chapter, we review the current advancement of cirRNAs with regard to their biogenesis, biological functions, gene regulatory mechanisms, and implications in human diseases and summarize the recent studies on circRNAs as potential diagnostic and prognostic biomarkers based on existing knowledge.

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“…7 These intrinsic features confer complicated functions on circRNAs in human diseases including cancer. 8 Moreover, circRNAs have been reported to be promising diagnostic and prognostic markers in many cancers including pancreatic cancer, 9,10 and exhibit tissue/ developmental-stage-specific expression. The circRNAs expression profile has been revealed in PDAC tissue 11,12 and plasma.…”

Section: Introductionmentioning

confidence: 99%

<p>Blocking circ_0013912 Suppressed Cell Growth, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells in vitro and in vivo Partially Through Sponging miR-7-5p</p>

Guo

Zhao

Wei

et al. 2020

CMAR

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Background: Circular RNAs have been emerging as biomarkers in diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC). The hsa_circ_0013912 (circ_0013912) has been retrieved to be upregulated in PDAC. Here, we further investigated its role in PDAC cells, as well as its mechanism via serving as competing endogenous RNA (ceRNA) for miRNA (miR)-7-5p, which is abundant in pancreas and suppresses the development of PDAC. Materials and Methods: The clinical human tissues were harvested from Gene Expression Omnibus (GEO) database and PDAC patients, and expression of circ_0013912 and miR-7-5p was detected by real-time quantitative PCR. The interaction between both was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and biotin-miRNA pull-down assay. Functional experiments were performed using Cell Counting Kit-8 assay, colony formation assay, fluorescence-activated cell separation method, caspase 3 activity assay kit, Western blotting, transwell assays, and xenograft tumor model. Results: circ_0013912 was upregulated in PDAC tumors and cells; besides, circ_0013912 upregulation was associated with TNM stage and lymph node metastasis. Silencing circ_0013912 inhibited cell viability, colony formation ability, cell cycle entrance, migration and invasion, but facilitated apoptosis rate and caspase 3 activity in PANC-1 and AsPC-1 cells, accompanied with decreased c-myc, cyclin D1 and vimentin, and increased E-cadherin. Furthermore, miR-7-5p was a target of circ_0013912. Blocking miR-7-5p could promote cell growth, migration and invasion of PANC-1 and AsPC-1 cells with circ_0013912 silencing or not. Tumor growth was also restrained by circ_0013912 downregulation. Conclusion: Circ_0013912 knockdown could suppress cell growth and metastasis of PDAC cells via sponging miR-7-5p.

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The roles of circular RNAs in human development and diseases

Cited by 88 publications

References 104 publications

Integrating multiple microarray dataset analysis and machine learning methods to reveal the key genes and regulatory mechanisms underlying human intervertebral disc degeneration

Integrating multiple microarray dataset analysis and machine learning methods to reveal the key genes and regulatory mechanisms underlying human intervertebral disc degeneration

Circular RNAs and Its Biological Functions in Health and Disease

<p>Blocking circ_0013912 Suppressed Cell Growth, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells in vitro and in vivo Partially Through Sponging miR-7-5p</p>

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