title: Identification of miRNA, lncRNA and mRNA-associated ceRNA networks and potential biomarker for MELAS with mitochondrial DNA A3243G mutation.
abstract: Researchers in the field of mitochondrial biology are increasingly unveiling of the complex mechanisms between mitochondrial dysfunction and noncoding RNAs (ncRNAs). However, roles of ncRNAs underlying mitochondrial myopathy remain unexplored. The aim of this study was to elucidate the regulating networks of dysregulated ncRNAs in Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) with mitochondrial DNA (mtDNA) A3243G mutation, which might make contributions to the unveiling of the complex mechanisms underlying mitochondrial myopathy and, possibly, new tools applicable to clinical practice. Through high-throughput technology followed by quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics analyses, for the first time, we found that the dysregulated muscle miRNAs and lncRNAs between 20 MELAS patients with mtDNA A3243G mutation and 20 controls formed complex regulation networks and participated in immune system, signal transduction, translation, muscle contraction and other pathways in discovery and training phase. Then, selected ncRNAs were validated in muscle and serum in independent validation cohorts by qRT-PCR. Finally, ROC curve analysis indicated reduced serum miR-27b-3p had the better diagnosis value than lactate and might serve as a novel, noninvasive biomarker for MELAS. Follow-up investigation is warranted to better understand roles of ncRNAs in mitochondrial myopathy pathogenesis.
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Bioengineering, Qilu University of Technology, Jinan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Kunqian
authors.initials: K
authors.lastname: Ji
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wen
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Yan
mesh_terms: D000483:Alleles; D015415:Biomarkers; D001706:Biopsy; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods; D004272:DNA, Mitochondrial; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005838:Genotype; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics*; D035683:MicroRNAs; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger