Issue
Identification of atrial fibrillation-related circular RNAs and constructing the integrative regulatory network of circular RNAs, microRNAs and mRNAs by bioinformatics analysis
Corresponding Author(s) : Juxiang Li
Cellular and Molecular Biology,
Vol. 66 No. 7: Issue 7
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- Kim D, Yang P-S, Jang E, Yu HT, Kim T-H, Uhm J-S, Kim J-Y, Pak H-N, Lee M-H, Joung B. 10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population. Am Heart J. 2018; 202: 20-26.
- Padfield GJ, Steinberg C, Swampillai J, Qian H, Connolly SJ, Dorian P, Green MS, Humphries KH, Klein GJ, Sheldon R. Progression of paroxysmal to persistent atrial fibrillation: 10-year follow-up in the Canadian Registry of Atrial Fibrillation. Heart Rhythm. 2017; 14(6): 801-807.
- Jin M-N, Kim T-H, Kang K-W, Yu HT, Uhm J-S, Joung B, Lee M-H, Kim E, Pak H-N. Atrial fibrillation catheter ablation improves 1-year follow-up cognitive function, especially in patients with impaired cognitive function. Circ Arrhythm Electrophysiol. 2019; 12(7): e007197.
- Modin D, Claggett B, Gislason G, Hansen ML, Worck R, Johannessen A, Hansen J, Svendsen JH, Pallisgaard JL, Schou M. Catheter ablation for atrial fibrillation is associated with lower incidence of heart failure and death. EP Europace. 2020; 22(1): 74-83.
- Yu HT, Kim IS, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN. Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation. J Cardiovasc Electrophysiol 2020; 31(2): 457-464.
- Boyle PM, Zghaib T, Zahid S, Ali RL, Deng D, Franceschi WH, Hakim JB, Murphy MJ, Prakosa A, Zimmerman SL. Computationally guided personalized targeted ablation of persistent atrial fibrillation. Nat Biomed Eng. 2019; 3(11): 870-879.
- Ang Y-S, Rajamani S, Haldar SM, Hüser J. A new therapeutic framework for atrial fibrillation drug development. Circ Rese. 2020; 127(1): 184-201.
- Wit AL, Wellens HJ, Josephson ME. Electrophysiological Foundations of Cardiac Arrhythmias: A Bridge Between Basic Mechanisms and Clinical Electrophysiology: Cardiotext Publishing; 2017.
- Cox T, Dwight J. Oxford Textbook of Medicine: Cardiovascular Disorders: Oxford University Press; 2016.
- Subic A, Cermakova P, Religa D, Han S, von Euler M, Kåreholt I, Johnell K, Fastbom J, Bognandi L, Winblad B. Treatment of atrial fibrillation in patients with dementia: A cohort study from the Swedish Dementia Registry. J Alzheimer's Dis. 2018; 61(3): 1119-1128.
- Akgül E. Investigation of the Effect of Preoperative Hypoalbuminemia, Blood Urea Nitrogen and Creatinine Levels on Postoperative Atrial Fibrillation on Off-Pump Coronary Bypass Surgery Patients. Paper presented at: The Heart Surgery Forum, 2020.
- Reiffel JA. Biomarkers and their relationship to atrial fibrillation: mechanisms, prognosis and management. Biomark Med 2019; 13: 1433–1438.
- Choi SH, Weng L-C, Roselli C, Lin H, Haggerty CM, Shoemaker MB, Barnard J, Arking DE, Chasman DI, Albert CM. Association between titin loss-of-function variants and early-onset atrial fibrillation. Jama. 2018; 320(22): 2354-2364.
- Heijman J, Guichard J-B, Dobrev D, Nattel S. Translational challenges in atrial fibrillation. Circ Res. 2018; 122(5): 752-773.
- Babapoor-Farrokhran S, Gill D, Rasekhi RT. The role of long noncoding RNAs in atrial fibrillation. Heart Rhythm. 2020: 1–27.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, D K. An overview of genome editing methods based on endonucleases. Mod Genet J. 2020; 15(2): 75-92.
- He L, Zhang A, Xiong L, Li Y, Huang R, Liao L, Zhu Z. Deep circular RNA sequencing provides insights into the mechanism underlying grass carp reovirus infection. Int J Mol Sci 2017; 18(9): 1977.
- Zhang Y, Ke X, Liu J, Ma X, Liu Y, Liang D, Wang L, Guo C, Luo Y. Characterization of circRNA"‘associated ceRNA networks in patients with nonvalvular persistent atrial fibrillation. Mol Med Rep. 2019; 19(1): 638-650.
- Stć™pieÅ„ E, Costa MC, Kurc S, Drożdż A, Cortez-Dias N, Enguita FJ. The circulating non-coding RNA landscape for biomarker research: lessons and prospects from cardiovascular diseases. Acta Pharmacol Sin. 2018; 39(7): 1085-1099.
- Costa MC, Cortez-Dias N, Gabriel A, de Sousa J, Fiúza M, Gallego J, Nobre í‚, Pinto FJ, Enguita FJ. circRNA-miRNA cross-talk in the transition from paroxysmal to permanent atrial fibrillation. Int J Cardiol. 2019; 290: 134-137.
- Nan A, Chen L, Zhang N, Liu Z, Yang T, Wang Z, Yang C, Jiang Y. A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis. Arch Toxicol. 2017; 91(4): 1671-1684.
- Karagkouni D, Paraskevopoulou MD, Chatzopoulos S, Vlachos IS, Tastsoglou S, Kanellos I, Papadimitriou D, Kavakiotis I, Maniou S, Skoufos G. DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA–gene interactions. Nucleic Acids Res. 2018; 46(D1): D239-D245.
- Du J, Yuan Z, Ma Z, Song J, Xie X, Chen Y. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol Biosyst. 2014; 10(9): 2441-2447.
- Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011; 146(3): 353-358.
- Scardoni G, Petterlini M, Laudanna C. Analyzing biological network parameters with CentiScaPe. Bioinformatics. 2009; 25(21): 2857-2859.
- Wang J, Li Z, Du J, Li J, Zhang Y, Liu J, Hou Y. The expression profile analysis of atrial mRNA in rats with atrial fibrillation: the role of IGF1 in atrial fibrosis. BMC Cardiovasc Disord. 2019; 19(19): 40–11.
- Zhang L, Liu L, Ma M, Cheng S, Cheng B, Li P, Wen Y, Du Y, Liang X, Zhao Y. Integrative analysis of transcriptome-wide association study data and mRNA expression profiles identified candidate genes and pathways associated with atrial fibrillation. Heart and Vessels. 2019; 34(34): 1882-1888.
- Ebbesen KK, Kjems J, Hansen TB. Circular RNAs: identification, biogenesis and function. Biochim Biophys Acta 2016; 1859(1): 163-168.
- Chen Y, Li C, Tan C, Liu X. Circular RNAs: a new frontier in the study of human diseases. J Med Genet. 2016; 53(6): 359-365.
- Zhang J, Xu Y, Xu S, Liu Y, Yu L, Li Z, Xue X, Wang H. Plasma circular RNAs, Hsa_circRNA_025016, predict postoperative atrial fibrillation after isolated off"pump coronary artery bypass grafting. J Am Heart Ass. 2018; 7(2): e006642.
- Jia YC, Wang JY, Liu YY, Li B, Guo H, Zang AM. LncRNA MAFG"AS1 facilitates the migration and invasion of NSCLC cell via sponging miR"339"5p from MMP15. Cell Biol Int. 2019; 43(4): 384-393.
- Wang J, Jiang M, Xia S. miR-339-5p increases radiosensitivity of lung cancer cells by targeting phosphatases of regenerating liver-1 (PRL-1). Med Sci Monit. 2018; 24: 8408.
- Zhang L, Xia H, Zhao C, Shi L, Ren X. Cyclic RNA hsa_circ_0091017 inhibits proliferation, migration and invasiveness of bladder cancer cells by binding to microRNA-589-5p. Eur Rev Med Pharmacol Sci. 2020; 24(1): 86-96.
- Guo W-h, Wang X, Shang M-s, Chen Z, Guo Q, Li L, Wang H-y, Yu R-h, Ma C-s. Crosstalk between PKC and MAPK pathway activation in cardiac fibroblasts in a rat model of atrial fibrillation. Biotechnol Lett. 2020; 26: 1-9.
- Chen Z, Zuo X, Zhang Y, Han G, Zhang L, Wu J, Wang X. MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect. Cell Death Dis. 2018; 9(5): 1-14.
- Maharry SE, Walker CJ, Liyanarachchi S, Mehta S, Patel M, Bainazar MA, Huang X, Lankenau MA, Hoag KW, Ranganathan P. Dissection of the major hematopoietic quantitative trait locus in chromosome 6q23. 3 identifies miR-3662 as a player in hematopoiesis and acute myeloid leukemia. Cancer Discov. 2016; 6(9): 1036-1051.
- Feng DD, Zhang H, Zhang P, Zheng YS, Zhang XJ, Han BW, Luo XQ, Xu L, Zhou H, Qu LH. Down"regulated miR"331–5p and miR"27a are associated with chemotherapy resistance and relapse in leukaemia. J Cell Mol Med. 2011; 15(10): 2164-2175.
References
Kim D, Yang P-S, Jang E, Yu HT, Kim T-H, Uhm J-S, Kim J-Y, Pak H-N, Lee M-H, Joung B. 10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population. Am Heart J. 2018; 202: 20-26.
Padfield GJ, Steinberg C, Swampillai J, Qian H, Connolly SJ, Dorian P, Green MS, Humphries KH, Klein GJ, Sheldon R. Progression of paroxysmal to persistent atrial fibrillation: 10-year follow-up in the Canadian Registry of Atrial Fibrillation. Heart Rhythm. 2017; 14(6): 801-807.
Jin M-N, Kim T-H, Kang K-W, Yu HT, Uhm J-S, Joung B, Lee M-H, Kim E, Pak H-N. Atrial fibrillation catheter ablation improves 1-year follow-up cognitive function, especially in patients with impaired cognitive function. Circ Arrhythm Electrophysiol. 2019; 12(7): e007197.
Modin D, Claggett B, Gislason G, Hansen ML, Worck R, Johannessen A, Hansen J, Svendsen JH, Pallisgaard JL, Schou M. Catheter ablation for atrial fibrillation is associated with lower incidence of heart failure and death. EP Europace. 2020; 22(1): 74-83.
Yu HT, Kim IS, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN. Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation. J Cardiovasc Electrophysiol 2020; 31(2): 457-464.
Boyle PM, Zghaib T, Zahid S, Ali RL, Deng D, Franceschi WH, Hakim JB, Murphy MJ, Prakosa A, Zimmerman SL. Computationally guided personalized targeted ablation of persistent atrial fibrillation. Nat Biomed Eng. 2019; 3(11): 870-879.
Ang Y-S, Rajamani S, Haldar SM, Hüser J. A new therapeutic framework for atrial fibrillation drug development. Circ Rese. 2020; 127(1): 184-201.
Wit AL, Wellens HJ, Josephson ME. Electrophysiological Foundations of Cardiac Arrhythmias: A Bridge Between Basic Mechanisms and Clinical Electrophysiology: Cardiotext Publishing; 2017.
Cox T, Dwight J. Oxford Textbook of Medicine: Cardiovascular Disorders: Oxford University Press; 2016.
Subic A, Cermakova P, Religa D, Han S, von Euler M, Kåreholt I, Johnell K, Fastbom J, Bognandi L, Winblad B. Treatment of atrial fibrillation in patients with dementia: A cohort study from the Swedish Dementia Registry. J Alzheimer's Dis. 2018; 61(3): 1119-1128.
Akgül E. Investigation of the Effect of Preoperative Hypoalbuminemia, Blood Urea Nitrogen and Creatinine Levels on Postoperative Atrial Fibrillation on Off-Pump Coronary Bypass Surgery Patients. Paper presented at: The Heart Surgery Forum, 2020.
Reiffel JA. Biomarkers and their relationship to atrial fibrillation: mechanisms, prognosis and management. Biomark Med 2019; 13: 1433–1438.
Choi SH, Weng L-C, Roselli C, Lin H, Haggerty CM, Shoemaker MB, Barnard J, Arking DE, Chasman DI, Albert CM. Association between titin loss-of-function variants and early-onset atrial fibrillation. Jama. 2018; 320(22): 2354-2364.
Heijman J, Guichard J-B, Dobrev D, Nattel S. Translational challenges in atrial fibrillation. Circ Res. 2018; 122(5): 752-773.
Babapoor-Farrokhran S, Gill D, Rasekhi RT. The role of long noncoding RNAs in atrial fibrillation. Heart Rhythm. 2020: 1–27.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, D K. An overview of genome editing methods based on endonucleases. Mod Genet J. 2020; 15(2): 75-92.
He L, Zhang A, Xiong L, Li Y, Huang R, Liao L, Zhu Z. Deep circular RNA sequencing provides insights into the mechanism underlying grass carp reovirus infection. Int J Mol Sci 2017; 18(9): 1977.
Zhang Y, Ke X, Liu J, Ma X, Liu Y, Liang D, Wang L, Guo C, Luo Y. Characterization of circRNA"‘associated ceRNA networks in patients with nonvalvular persistent atrial fibrillation. Mol Med Rep. 2019; 19(1): 638-650.
Stć™pieÅ„ E, Costa MC, Kurc S, Drożdż A, Cortez-Dias N, Enguita FJ. The circulating non-coding RNA landscape for biomarker research: lessons and prospects from cardiovascular diseases. Acta Pharmacol Sin. 2018; 39(7): 1085-1099.
Costa MC, Cortez-Dias N, Gabriel A, de Sousa J, Fiúza M, Gallego J, Nobre í‚, Pinto FJ, Enguita FJ. circRNA-miRNA cross-talk in the transition from paroxysmal to permanent atrial fibrillation. Int J Cardiol. 2019; 290: 134-137.
Nan A, Chen L, Zhang N, Liu Z, Yang T, Wang Z, Yang C, Jiang Y. A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis. Arch Toxicol. 2017; 91(4): 1671-1684.
Karagkouni D, Paraskevopoulou MD, Chatzopoulos S, Vlachos IS, Tastsoglou S, Kanellos I, Papadimitriou D, Kavakiotis I, Maniou S, Skoufos G. DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA–gene interactions. Nucleic Acids Res. 2018; 46(D1): D239-D245.
Du J, Yuan Z, Ma Z, Song J, Xie X, Chen Y. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol Biosyst. 2014; 10(9): 2441-2447.
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011; 146(3): 353-358.
Scardoni G, Petterlini M, Laudanna C. Analyzing biological network parameters with CentiScaPe. Bioinformatics. 2009; 25(21): 2857-2859.
Wang J, Li Z, Du J, Li J, Zhang Y, Liu J, Hou Y. The expression profile analysis of atrial mRNA in rats with atrial fibrillation: the role of IGF1 in atrial fibrosis. BMC Cardiovasc Disord. 2019; 19(19): 40–11.
Zhang L, Liu L, Ma M, Cheng S, Cheng B, Li P, Wen Y, Du Y, Liang X, Zhao Y. Integrative analysis of transcriptome-wide association study data and mRNA expression profiles identified candidate genes and pathways associated with atrial fibrillation. Heart and Vessels. 2019; 34(34): 1882-1888.
Ebbesen KK, Kjems J, Hansen TB. Circular RNAs: identification, biogenesis and function. Biochim Biophys Acta 2016; 1859(1): 163-168.
Chen Y, Li C, Tan C, Liu X. Circular RNAs: a new frontier in the study of human diseases. J Med Genet. 2016; 53(6): 359-365.
Zhang J, Xu Y, Xu S, Liu Y, Yu L, Li Z, Xue X, Wang H. Plasma circular RNAs, Hsa_circRNA_025016, predict postoperative atrial fibrillation after isolated off"pump coronary artery bypass grafting. J Am Heart Ass. 2018; 7(2): e006642.
Jia YC, Wang JY, Liu YY, Li B, Guo H, Zang AM. LncRNA MAFG"AS1 facilitates the migration and invasion of NSCLC cell via sponging miR"339"5p from MMP15. Cell Biol Int. 2019; 43(4): 384-393.
Wang J, Jiang M, Xia S. miR-339-5p increases radiosensitivity of lung cancer cells by targeting phosphatases of regenerating liver-1 (PRL-1). Med Sci Monit. 2018; 24: 8408.
Zhang L, Xia H, Zhao C, Shi L, Ren X. Cyclic RNA hsa_circ_0091017 inhibits proliferation, migration and invasiveness of bladder cancer cells by binding to microRNA-589-5p. Eur Rev Med Pharmacol Sci. 2020; 24(1): 86-96.
Guo W-h, Wang X, Shang M-s, Chen Z, Guo Q, Li L, Wang H-y, Yu R-h, Ma C-s. Crosstalk between PKC and MAPK pathway activation in cardiac fibroblasts in a rat model of atrial fibrillation. Biotechnol Lett. 2020; 26: 1-9.
Chen Z, Zuo X, Zhang Y, Han G, Zhang L, Wu J, Wang X. MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect. Cell Death Dis. 2018; 9(5): 1-14.
Maharry SE, Walker CJ, Liyanarachchi S, Mehta S, Patel M, Bainazar MA, Huang X, Lankenau MA, Hoag KW, Ranganathan P. Dissection of the major hematopoietic quantitative trait locus in chromosome 6q23. 3 identifies miR-3662 as a player in hematopoiesis and acute myeloid leukemia. Cancer Discov. 2016; 6(9): 1036-1051.
Feng DD, Zhang H, Zhang P, Zheng YS, Zhang XJ, Han BW, Luo XQ, Xu L, Zhou H, Qu LH. Down"regulated miR"331–5p and miR"27a are associated with chemotherapy resistance and relapse in leukaemia. J Cell Mol Med. 2011; 15(10): 2164-2175.