Abnormalities of hsa-mir-16 and hsa-mir-124 Affect Mitochondrial Function
and Fatty Acid Metabolism in Tetralogy of Fallot

Yue      Yu; Xing      Ge; Lu-Shan      Wang; Xu-Xu      Wang; Li-Chun      Xu

doi:10.2174/1386207325666220421104617

Abstract

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease in clinical practice. It is mainly due to cardiovascular hypoplasia during embryonic development. The study aimed to find the etiology of TOF.

Methods: Through the mRNA expression profile analysis of the GSE35776 dataset, differentially expressed genes (DEGs) were found, and the functional analysis and protein-protein interaction (PPI) network analysis were then performed on DEGs. Likewise, the hub genes and functional clusters of DEGs were analyzed using the PPI network. Differentially expressed miRNAs were analyzed from the GSE35490 dataset, followed by miRNet predicted transcription factors (TFs) and target genes. The key TF-miRNA-gene interaction mechanism was explored through the found significant difference between genes and target genes.

Results: A total of 191 differentially expressed genes and 57 differentially expressed miRNAs were identified. The main mechanisms involved in TOF were mitochondria-related and energy metabolism- related molecules and pathways in GO and KEGG analysis. This discovery was identical in TFs and target genes. The key miRNAs, hsa-mir-16 and hsa-mir-124, were discovered by the Venn diagram. A co-expression network with the mechanism of action centered on two miRNAs was made.

Conclusion: Hsa-mir-16 and hsa-mir-124 are the key miRNAs of TOF, which mainly regulate the expression of NT5DC1, ECHDC1, HSDL2, FCHO2, and ACAA2 involved in the conversion of ATP in the mitochondria and the metabolic rate of fatty acids (FA). Our research provides key molecules and pathways into the etiology of TOF, which can be used as therapeutic targets.

Keywords: Tetralogy of fallot, bioinformatics analysis, biomarkers, pathways, microRNA, co-expression network.

« Previous Next »

Graphical Abstract

[1]
Wise-Faberowski, L.; Asija, R.; McElhinney, D.B. Tetralogy of fallot: Everything you wanted to know but were afraid to ask. Paediatr. Anaesth.,  2019, 29(5), 475-482.
 [http://dx.doi.org/10.1111/pan.13569] [PMID:  30592107]

[2]
Poon, L.C.Y.; Huggon, I.C.; Zidere, V.; Allan, L.D. Tetralogy of fallot in the fetus in the current era. Ultrasound Obstet. Gynecol.,  2007, 29(6), 625-627.
 [http://dx.doi.org/10.1002/uog.3971] [PMID:  17405110]

[3]
Morgenthau, A.; Frishman, W.H. Genetic origins of tetralogy of fallot. Cardiol. Rev.,  2018, 26(2), 86-92.
 [http://dx.doi.org/10.1097/CRD.0000000000000170] [PMID:  29045289]

[4]
Sabri, M.R.; Gharipour, M.; Tayebi, N.; Sadeghian, L.; Javanmard, S.H.; Sarrafzadegan, N. Determin-ing genetic variants in children and adolescents suffering from tetralogy of Fallot with a positive fami-ly history: Methodology. Acta Biomed.,  2020, 91(4), e2020096.
 [PMID:  33525261]

[5]
Lee, W.; Smith, R.S.; Comstock, C.H.; Kirk, J.S.; Riggs, T.; Weinhouse, E. Tetralogy of fallot: Prenatal diagnosis and postnatal survival. Obstet. Gynecol.,  1995, 86(4 Pt 1), 583-588.
 [http://dx.doi.org/10.1016/0029-7844(95)00245-M] [PMID:  7675384]

[6]
Zhao, Y.; Abuhamad, A.; Fleenor, J.; Guo, Y.; Zhang, W.; Cao, D.; Zeng, S.; Sinkovskaya, E.; Zhou, Q. Prenatal and postnatal survival of fetal tetralogy of fallot: A meta-analysis of perinatal outcomes and associated genetic disorders. J. Ultrasound Med.,  2016, 35(5), 905-915.
 [http://dx.doi.org/10.7863/ultra.15.04055] [PMID:  27022172]

[7]
Manzoni, C.; Kia, D.A.; Vandrovcova, J.; Hardy, J.; Wood, N.W.; Lewis, P.A.; Ferrari, R. Ge-nome, transcriptome and proteome: The rise of omics data and their integration in biomedical sciences. Brief. Bioinform.,  2018, 19(2), 286-302.
 [http://dx.doi.org/10.1093/bib/bbw114] [PMID:  27881428]

[8]
Grunert, M.; Appelt, S.; Dunkel, I.; Berger, F.; Sperling, S.R. Altered microRNA and target gene ex-pression related to tetralogy of fallot. Sci. Rep.,  2019, 9(1), 19063.
 [http://dx.doi.org/10.1038/s41598-019-55570-4] [PMID:  31836860]

[9]
Wang, B.; Shi, G.; Zhu, Z.; Chen, H.; Fu, Q. Sexual difference of small RNA expression in tetral-ogy of fallot. Sci. Rep.,  2018, 8(1), 12847.
 [http://dx.doi.org/10.1038/s41598-018-31243-6] [PMID:  30150777]

[10]
Gu, Q.; Chen, X-T.; Xiao, Y-B.; Chen, L.; Wang, X-F.; Fang, J.; Chen, B-C.; Hao, J. Identifica-tion of differently expressed genes and small molecule drugs for tetralogy of fallot by bioinformatics strategy. Pediatr. Cardiol.,  2014, 35(5), 863-869.
 [http://dx.doi.org/10.1007/s00246-014-0868-8] [PMID:  24463614]

[11]
Guo, T.; Repetto, G.M.; McDonald McGinn, D.M.; Chung, J.H.; Nomaru, H.; Campbell, C.L.; Blon-ska, A.; Bassett, A.S.; Chow, E.W.C.; Mlynarski, E.E.; Swillen, A.; Vermeesch, J.; Devriendt, K.; Gothelf, D.; Carmel, M.; Michaelovsky, E.; Schneider, M.; Eliez, S.; Antonarakis, S.E.; Coleman, K.; Tomita-Mitchell, A.; Mitchell, M.E.; Digilio, M.C.; Dallapiccola, B.; Marino, B.; Philip, N.; Busa, T.; Kushan-Wells, L.; Bearden, C.E.; Piotrowicz, M.; Hawuła, W.; Roberts, A.E.; Tassone, F.; Simon, T.J.; van Duin, E.D.A.; van Amelsvoort, T.A.; Kates, W.R.; Zackai, E.; Johnston, H.R.; Cutler, D.J.; Agopian, A.J.; Goldmuntz, E.; Mitchell, L.E.; Wang, T.; Emanuel, B.S.; Morrow, B.E. International 22q11.2 Consorti-um/Brain and Behavior Consortium*. Genome-wide association study to find mod-ifiers for tetralogy of fallot in the 22q11.2 deletion syndrome identifies variants in the GPR98 locus on 5q14.3. Circ. Cardiovasc. Genet.,  2017, 10(5), e001690.
 [http://dx.doi.org/10.1161/CIRCGENETICS.116.001690] [PMID:  29025761]

[12]
Zhuang, B.; Hu, Y.; Fan, X.; Li, M.; Zhu, J.; Liu, H.; Cao, L.; Liang, D.; Zhang, J.; Yu, Z.; Han, S. Peptidomic analysis of maternal serum to identify biomarker candidates for prenatal diagnosis of tetralogy of fallot. J. Cell. Biochem.,  2018, 119(1), 468-477.
 [http://dx.doi.org/10.1002/jcb.26204] [PMID:  28598000]

[13]
Xia, Y.; Hong, H.; Ye, L.; Wang, Y.; Chen, H.; Liu, J. Label-free quantitative proteomic analysis of right ventricular remodeling in infant tetralogy of fallot patients. J. Proteomics,  2013, 84, 78-91.
 [http://dx.doi.org/10.1016/j.jprot.2013.03.032] [PMID:  23571024]

[14]
O’Brien, J.E., Jr; Kibiryeva, N.; Zhou, X-G.; Marshall, J.A.; Lofland, G.K.; Artman, M.; Chen, J.; Bit-tel, D.C. Noncoding RNA expression in myocardium from infants with tetralogy of fallot. Circ. Cardiovasc. Genet.,  2012, 5(3), 279-286.
 [http://dx.doi.org/10.1161/CIRCGENETICS.111.961474] [PMID:  22528145]

[15]
Gautier, L.; Cope, L.; Bolstad, B.M.; Irizarry, R.A. affy-analysis of affymetrix genechip data at the probe level. Bioinformatics,  2004, 20(3), 307-315.
 [http://dx.doi.org/10.1093/bioinformatics/btg405] [PMID:  14960456]

[16]
Bolstad, B.M.; Irizarry, R.A.; Astrand, M.; Speed, T.P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics,  2003, 19(2), 185-193.
 [http://dx.doi.org/10.1093/bioinformatics/19.2.185] [PMID:  12538238]

[17]
Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers dif-feren-tial expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res.,  2015, 43(7), e47.
 [http://dx.doi.org/10.1093/nar/gkv007] [PMID:  25605792]

[18]
Chen, L.; Zhang, Y-H.; Wang, S.; Zhang, Y.; Huang, T.; Cai, Y-D. Prediction and analysis of es-sen-tial genes using the enrichments of gene ontology and KEGG pathways. PLoS One,  2017, 12(9), e0184129.
 [http://dx.doi.org/10.1371/journal.pone.0184129] [PMID:  28873455]

[19]
Gene Ontology Consortium. Gene ontology consortium: Going forward. Nucleic Acids Res.,  2015, 43(Database issue), D1049-D1056.
 [PMID:  25428369]

[20]
Kanehisa, M.; Sato, Y. KEGG Mapper for inferring cellular functions from protein sequences. Protein Sci.,  2020, 29(1), 28-35.
 [http://dx.doi.org/10.1002/pro.3711] [PMID:  31423653]

[21]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C.V. STRING v11: protein-protein asso-cia-tion networks with increased coverage, supporting functional discovery in genome-wide experi-mental da-tasets. Nucleic Acids Res.,  2019, 47(D1), D607-D613.
 [http://dx.doi.org/10.1093/nar/gky1131] [PMID:  30476243]

[22]
Kumar, U.S.; Kumar, T.D.; Siva, R.; Doss, G.P.C.; Younes, S.; Younes, N.; Sidenna, M.; Zayed, H. Dysregulation of signaling pathways due to differentially expressed genes from the b-cell tran-scriptomes of systemic lupus erythematosus patients - A bioinformatics approach. Front. Bioeng. Biotechnol.,  2020, 8, 276.
 [http://dx.doi.org/10.3389/fbioe.2020.00276] [PMID:  32426333]

[23]
Chang, L.; Zhou, G.; Soufan, O.; Xia, J. miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res.,  2020, 48(W1), W244-W251.
 [http://dx.doi.org/10.1093/nar/gkaa467] [PMID:  32484539]

[24]
Donti, T.R.; Stromberger, C.; Ge, M.; Eldin, K.W.; Craigen, W.J.; Graham, B.H. Screen for ab-normal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase defi-ciency and mtDNA depletion. Dis. Model. Mech.,  2014, 7(2), 271-280.
 [PMID:  24271779]

[25]
Raggi, F.; Cangelosi, D.; Becherini, P.; Blengio, F.; Morini, M.; Acquaviva, M.; Belli, M.L.; Panizzon, G.; Cervo, G.; Varesio, L.; Eva, A.; Bosco, M.C. Transcriptome analysis defines myocardi-um gene signa-tures in children with ToF and ASD and reveals disease-specific molecular reprogram-ming in response to surgery with cardiopulmonary bypass. J. Transl. Med.,  2020, 18(1), 21.
 [http://dx.doi.org/10.1186/s12967-020-02210-5] [PMID:  31924244]

[26]
Kumar, S.U.; Kumar, D.T.; Siva, R.; Doss, C.G.P.; Zayed, H. Integrative bioinformatics ap-proaches to map potential novel genes and pathways involved in ovarian cancer. Front. Bioeng. Biotechnol.,  2019, 7, 391.
 [http://dx.doi.org/10.3389/fbioe.2019.00391] [PMID:  31921802]

[27]
Semenza, G.L. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu. Rev. Pathol.,  2014, 9, 47-71.
 [http://dx.doi.org/10.1146/annurev-pathol-012513-104720] [PMID:  23937437]

[28]
Shults, N.V.; Melnyk, O.; Suzuki, D.I.; Suzuki, Y.J. Redox biology of right-sided heart failure. Antioxidants,  2018, 7(8), E106.
 [http://dx.doi.org/10.3390/antiox7080106] [PMID:  30096794]

[29]
Shinde, S.B.; Save, V.C.; Patil, N.D.; Mishra, K.P.; Tendolkar, A.G. Impairment of mitochondri-al respiratory chain enzyme activities in tetralogy of fallot. Clin. Chim. Acta,  2007, 377(1-2), 138-143.
 [http://dx.doi.org/10.1016/j.cca.2006.09.011] [PMID:  17084831]

[30]
Gao, K.; Zhang, J.; Gao, P.; Wang, Q.; Liu, Y.; Liu, J.; Zhang, Y.; Li, Y.; Chang, H.; Ren, P.; Liu, J.; Wang, Y.; Wang, W. Qishen granules exerts cardioprotective effects on rats with heart failure via regulat-ing fatty acid and glucose metabolism. Chin. Med.,  2020, 15, 21.
 [http://dx.doi.org/10.1186/s13020-020-0299-9] [PMID:  32158496]

[31]
Akhmedov, A.T.; Rybin, V.; Marín-García, J. Mitochondrial oxidative metabolism and uncou-pling proteins in the failing heart. Heart Fail. Rev.,  2015, 20(2), 227-249.
 [http://dx.doi.org/10.1007/s10741-014-9457-4] [PMID:  25192828]

[32]
Bittle, G.J.; Morales, D.; Pietris, N.; Parchment, N.; Parsell, D.; Peck, K.; Deatrick, K.B.; Rodri-guez-Borlado, L.; Smith, R.R.; Marbán, L.; Kaushal, S. Exosomes isolated from human cardiosphere-derived cells attenuate pressure overload-induced right ventricular dysfunction. J. Thorac. Cardiovasc. Surg.,  2021, 162(3), 975-986.
 [PMID:  33046229]

[33]
Liu, L.; Chen, Y.; Shu, J.; Tang, C.E.; Jiang, Y.; Luo, F. Identification of microRNAs enriched in ex-osomes in human pericardial fluid of patients with atrial fibrillation based on bioinformatic analy-sis. J. Thorac. Dis.,  2020, 12(10), 5617-5627.
 [http://dx.doi.org/10.21037/jtd-20-2066] [PMID:  33209394]

[34]
Pasta, S.; Agnese, V.; Gallo, A.; Cosentino, F.; Di Giuseppe, M.; Gentile, G.; Raffa, G.M.; Maalouf, J.F.; Michelena, H.I.; Bellavia, D.; Conaldi, P.G.; Pilato, M. Shear stress and aortic strain as-sociations with biomarkers of ascending thoracic aortic aneurysm. Shear stress and aortic strain associ-ations with bi-omarkers of ascending thoracic aortic aneurysm. Ann. Thorac. Surg.,  2020, 110(5), 1595-1604.
 [http://dx.doi.org/10.1016/j.athoracsur.2020.03.017] [PMID:  32289298]

[35]
Trac, D.; Maxwell, J.T.; Brown, M.E.; Xu, C.; Davis, M.E. Aggregation of child cardiac progeni-tor cells into spheres activates notch signaling and improves treatment of right ventricular heart failure. Circ. Res.,  2019, 124(4), 526-538.
 [http://dx.doi.org/10.1161/CIRCRESAHA.118.313845] [PMID:  30590978]

[36]
Papa, S.; Martino, P.L.; Capitanio, G.; Gaballo, A.; De Rasmo, D.; Signorile, A.; Petruzzella, V. The oxidative phosphorylation system in mammalian mitochondria. Adv. Exp. Med. Biol.,  2012, 942, 3-37.
 [http://dx.doi.org/10.1007/978-94-007-2869-1_1] [PMID:  22399416]

[37]
Sano, H.I.; Toki, T.; Naito, Y.; Tomita, M. Developmental changes in the balance of glycolytic ATP production and oxidative phosphorylation in ventricular cells: A simulation study. J. Theor. Biol.,  2017, 419, 269-277.
 [http://dx.doi.org/10.1016/j.jtbi.2017.02.019] [PMID:  28237394]

[38]
Barac, Y.D.; Emrich, F.; Krutzwakd-Josefson, E.; Schrepfer, S.; Sampaio, L.C.; Willerson, J.T.; Rob-bins, R.C.; Ciechanover, A.; Mohr, F.W.; Aravot, D.; Taylor, D.A. The ubiquitin-proteasome sys-tem: A potential therapeutic target for heart failure. J. Heart Lung Transplant.,  2017, 36(7), 708-714.
 [http://dx.doi.org/10.1016/j.healun.2017.02.012] [PMID:  28341100]

[39]
Horikoshi, Y.; Yan, Y.; Terashvili, M.; Wells, C.; Horikoshi, H.; Fujita, S.; Bosnjak, Z.J.; Bai, X. Fatty acid-treated induced pluripotent stem cell-derived human cardiomyocytes exhibit adult cardio-myocyte-like energy metabolism phenotypes. Cells,  2019, 8(9), e1095.
 [http://dx.doi.org/10.3390/cells8091095] [PMID:  31533262]

[40]
Li, T.; Zhang, Z.; Kolwicz, S.C., Jr; Abell, L.; Roe, N.D.; Kim, M.; Zhou, B.; Cao, Y.; Ritterhoff, J.; Gu, H.; Raftery, D.; Sun, H.; Tian, R. Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury. Cell Metab.,  2017, 25(2), 374-385.
 [http://dx.doi.org/10.1016/j.cmet.2016.11.005] [PMID:  28178567]

[41]
Mackey, R.H.; Kuller, L.H.; Moreland, L.W. Cardiovascular disease risk in patients with rheu-matic diseases. Clin. Geriatr. Med.,  2017, 33(1), 105-117.
 [http://dx.doi.org/10.1016/j.cger.2016.08.008] [PMID:  27886692]

[42]
Gong, J.; Sheng, W.; Ma, D.; Huang, G.; Liu, F. DNA methylation status of TBX20 in patients with tetralogy of fallot. BMC Med. Genomics,  2019, 12(1), 75.
 [http://dx.doi.org/10.1186/s12920-019-0534-3] [PMID:  31138201]

[43]
Gu, R.; Xu, J.; Lin, Y.; Sheng, W.; Ma, D.; Ma, X.; Huang, G. The role of histone modification and a regulatory single-nucleotide polymorphism (rs2071166) in the Cx43 promoter in patients with TOF. Sci. Rep.,  2017, 7(1), 10435.
 [http://dx.doi.org/10.1038/s41598-017-10756-6] [PMID:  28874875]

[44]
Thomford, N.E.; Dzobo, K.; Yao, N.A.; Chimusa, E.; Evans, J.; Okai, E.; Kruszka, P.; Muenke, M.; Awandare, G.; Wonkam, A.; Dandara, C. Genomics and epigenomics of congenital heart defects: Expert review and lessons learned in Africa. OMICS,  2018, 22(5), 301-321.
 [http://dx.doi.org/10.1089/omi.2018.0033] [PMID:  29762087]

[45]
Li, P.; Ge, J.; Li, H. Lysine acetyltransferases and lysine deacetylases as targets for cardiovascu-lar disease. Nat. Rev. Cardiol.,  2020, 17(2), 96-115.
 [http://dx.doi.org/10.1038/s41569-019-0235-9] [PMID:  31350538]

[46]
Kumarswamy, R.; Thum, T. Non-coding RNAs in cardiac remodeling and heart failure. Circ. Res.,  2013, 113(6), 676-689.
 [http://dx.doi.org/10.1161/CIRCRESAHA.113.300226] [PMID:  23989712]

[47]
Hinton, R.B.; Ware, S.M. Heart failure in pediatric patients with congenital heart disease. Circ. Res.,  2017, 120(6), 978-994.
 [http://dx.doi.org/10.1161/CIRCRESAHA.116.308996] [PMID:  28302743]

[48]
Zhang, J.; Chang, J.J.; Xu, F.; Ma, X.J.; Wu, Y.; Li, W.C.; Wang, H.J.; Huang, G.Y.; Ma, D. Mi-croRNA deregulation in right ventricular outflow tract myocardium in nonsyndromic tetralogy of fal-lot. Can. J. Cardiol.,  2013, 29(12), 1695-1703.
 [http://dx.doi.org/10.1016/j.cjca.2013.07.002] [PMID:  24140236]

[49]
Smith, T.; Rajakaruna, C.; Caputo, M.; Emanueli, C. MicroRNAs in congenital heart disease. Ann. Transl. Med.,  2015, 3(21), 333.
 [PMID:  26734643]

[50]
van den Akker, N.M.; Molin, D.G.; Peters, P.P.; Maas, S.; Wisse, L.J.; van Brempt, R.; van Mun-steren, C.J.; Bartelings, M.M.; Poelmann, R.E.; Carmeliet, P.; Gittenberger-de Groot, A.C. Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse em-bryos solely expressing the VEGF120 isoform. Circ. Res.,  2007, 100(6), 842-849.
 [http://dx.doi.org/10.1161/01.RES.0000261656.04773.39] [PMID:  17332426]

[51]
Grunert, M.; Dorn, C.; Schueler, M.; Dunkel, I.; Schlesinger, J.; Mebus, S.; Alexi-Meskishvili, V.; Per-rot, A.; Wassilew, K.; Timmermann, B.; Hetzer, R.; Berger, F.; Sperling, S.R. Rare and private variations in neural crest, apoptosis and sarcomere genes define the polygenic background of isolated tetralogy of fallot. Hum. Mol. Genet.,  2014, 23(12), 3115-3128.
 [http://dx.doi.org/10.1093/hmg/ddu021] [PMID:  24459294]

[52]
Gumus, G.; Giray, D.; Bobusoglu, O.; Tamer, L.; Karpuz, D.; Hallioglu, O. MicroRNA values in chil-dren with rheumatic carditis: A preliminary study. Rheumatol. Int.,  2018, 38(7), 1199-1205.
 [http://dx.doi.org/10.1007/s00296-018-4069-2] [PMID:  29845432]

[53]
Wicik, Z.; Eyileten, C.; Jakubik, D.; Simões, S.N.; Martins, D.C., Jr; Pavão, R.; Siller-Matula, J.M.; Postula, M. ACE2 interaction networks in covid-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors. J. Clin. Med.,  2020, 9(11), E3743.
 [http://dx.doi.org/10.3390/jcm9113743] [PMID:  33233425]

[54]
Padmanabhan, A.; Alexanian, M.; Linares-Saldana, R.; González-Terán, B.; Andreoletti, G.; Huang, Y.; Connolly, A.J.; Kim, W.; Hsu, A.; Duan, Q.; Winchester, S.A.B.; Felix, F.; Perez-Bermejo, J.A.; Wang, Q.; Li, L.; Shah, P.P.; Haldar, S.M.; Jain, R.; Srivastava, D. BRD4 (bromodomain-containing protein 4) interacts with gata4 (gata binding protein 4) to govern mitochondrial homeosta-sis in adult cardiomyocytes. Circulation,  2020, 142(24), 2338-2355.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047753] [PMID:  33094644]

[55]
Maréchal, L.; Sicotte, B.; Caron, V.; Brochu, M.; Tremblay, A. Fetal cardiac lipid sensing triggers an early and sex-related metabolic energy switch in intrauterine growth restriction. J. Clin. Endocrinol. Metab.,  2021, 106(11), 3295-3311.
 [http://dx.doi.org/10.1210/clinem/dgab496] [PMID:  34245263]

[56]
Wang, W.; Ledee, D. ACAA2 is a ligand-dependent coactivator for thyroid hormone receptor β1. Biochem. Biophys. Res. Commun.,  2021, 576, 15-21.
 [http://dx.doi.org/10.1016/j.bbrc.2021.08.073] [PMID:  34474245]

[57]
Christodoulou, C.C.; Zachariou, M.; Tomazou, M.; Karatzas, E.; Demetriou, C.A.; Zamba-Papanicolaou, E.; Spyrou, G.M. Investigating the transition of pre-symptomatic to symptomatic hunt-ing-ton’s disease status based on omics data. Int. J. Mol. Sci.,  2020, 21(19), E7414.
 [http://dx.doi.org/10.3390/ijms21197414] [PMID:  33049985]

[58]
Ma, L.; Umasankar, P.K.; Wrobel, A.G.; Lymar, A.; McCoy, A.J.; Holkar, S.S.; Jha, A.; Pradhan-Sundd, T.; Watkins, S.C.; Owen, D.J.; Traub, L.M. Transient fcho1/2⋅Eps15/R⋅AP-2 nanoclusters prime the AP-2 clathrin adaptor for cargo binding. Dev. Cell,  2016, 37(5), 428-443.
 [http://dx.doi.org/10.1016/j.devcel.2016.05.003] [PMID:  27237791]

[59]
Umasankar, P.K.; Sanker, S.; Thieman, J.R.; Chakraborty, S.; Wendland, B.; Tsang, M.; Traub, L.M. Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in develop-mental patterning. Nat. Cell Biol.,  2012, 14(5), 488-501.
 [http://dx.doi.org/10.1038/ncb2473] [PMID:  22484487]

[60]
Ghafouri-Fard, S.; Shoorei, H.; Bahroudi, Z.; Abak, A.; Majidpoor, J.; Taheri, M. An update on the role of miR-124 in the pathogenesis of human disorders. Biomed. Pharmacother.,  2021, 135, 111198.

[61]
Zheng, M-L.; Du, X-P.; Zhao, L.; Yang, X-C. Expression profile of circular RNAs in epicardial adi-pose tissue in heart failure. Chin. Med. J. (Engl.),  2020, 133(21), 2565-2572.
 [http://dx.doi.org/10.1097/CM9.0000000000001056] [PMID:  32852391]

[62]
Liu, H.; Zhang, B.; Chen, S.; Zhang, Y.; Ye, X.; Wei, Y.; Zhong, G.; Zhang, L. Identification of fer-roptosis-associated genes exhibiting altered expression in response to cardiopulmonary bypass dur-ing cor-rective surgery for pediatric tetralogy of fallot. Sci. Prog.,  2021, 104(4), 368504211050275.
 [http://dx.doi.org/10.1177/00368504211050275] [PMID:  34637369]

[63]
You, G.; Zu, B.; Wang, B.; Fu, Q.; Li, F. Identification of mirna-mrna-tfs regulatory network and crucial pathways involved in tetralogy of fallot. Front. Genet.,  2020, 11, 552.
 [http://dx.doi.org/10.3389/fgene.2020.00552] [PMID:  32595699]

[64]
Yu, H.; Wang, X.; Cao, H. Construction and investigation of a circRNA-associated ceRNA regu-lato-ry network in tetralogy of fallot. BMC Cardiovasc. Disord.,  2021, 21(1), 437.
 [http://dx.doi.org/10.1186/s12872-021-02217-w] [PMID:  34521346]

[65]
Zhang, X.; Gao, Y.; Zhang, X.; Zhang, X.; Xiang, Y.; Fu, Q.; Wang, B.; Xu, Z. FGD5-AS1 is a hub lncrna cerna in hearts with tetralogy of fallot which regulates congenital heart disease genes tran-scription-ally and epigenetically. Front. Cell Dev. Biol.,  2021, 9, 630634.
 [http://dx.doi.org/10.3389/fcell.2021.630634] [PMID:  34046402]

[66]
Ding, Y.; Gao, B.B.; Huang, J.Y. The role of mitochondrial DNA mutations in coronary heart disease. Eur. Rev. Med. Pharmacol. Sci.,  2020, 24(16), 8502-8509.
 [PMID:  32894556]

[67]
He, L.; Huang, C. MiR-19b and miR-16 cooperatively signaling target the regulator ADRA1A in hy-pertensive heart disease. Biomed. Pharmacother.,  2017, 91, 1178-1183.
 [http://dx.doi.org/10.1016/j.biopha.2017.04.041] [PMID:  28531963]

[68]
Liang, Y.P.; Liu, Q.; Xu, G.H.; Zhang, J.; Chen, Y.; Hua, F.Z.; Deng, C.Q.; Hu, Y.H. The lncRNA ROR/miR-124-3p/TRAF6 axis regulated the ischaemia reperfusion injury-induced inflamma-tory response in human cardiac myocytes. J. Bioenerg. Biomembr.,  2019, 51(6), 381-392.
 [http://dx.doi.org/10.1007/s10863-019-09812-9] [PMID:  31768721]

Rights & Permissions Print Cite

Article Metrics

7

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1386207325666220421104617	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Abnormalities of hsa-mir-16 and hsa-mir-124 Affect Mitochondrial Function and Fatty Acid Metabolism in Tetralogy of Fallot

Abstract Play Pause

Graphical Abstract

Related Journals

Abstract