title: Regulation of smooth muscle contractility by competing endogenous mRNAs in intracranial aneurysms.
abstract: Alterations in vascular smooth muscle cells (SMCs) contribute to the pathogenesis of intracranial aneurysms (IAs), but the genetic mechanisms underlying these alterations are unclear. We used microarray analysis to compare tissue small noncoding RNA and messenger RNA expression profiles in vessel wall samples from patients with late-stage IAs. We identified myocardin (MYOCD), a key contractility regulator of vascular SMCs, as a critical factor in IA progression. Using a multifaceted computational and experimental approach, we determined that depletion of competitive endogenous RNAs (ARHGEF12, FGF12, and ADCY5) enhanced factors that downregulate MYOCD, which induces the conversion of SMCs from differentiated contractile states into dedifferentiated phenotypes that exhibit enhanced proliferation, synthesis of new extracellular matrix, and organization of mural thrombi. These effects may lead to the repair and maintenance of IAs. This study presents guidelines for the prediction and validation of the IA regulator MYOCD in competitive endogenous RNA networks and facilitates the development of novel therapeutic and diagnostic tools for IAs.
authors: From the Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha (MZ, QZ, YP, QL, MY, YJ); Laboratory of Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University (YR, YW); and Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (YR, RW), Beijing, China.
authors: Mingming
authors: M
authors: Zhang
authors: Yuan
authors: Y
authors: Ren
authors: Yajie
authors: Y
authors: Wang
authors: Renzhi
authors: R
authors: Wang
authors: Qian
authors: Q
authors: Zhou
authors: Yong
authors: Y
authors: Peng
authors: Qi
authors: Q
authors: Li
authors: Mengqiang
authors: M
authors: Yu
authors: Yugang
authors: Y
authors: Jiang
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D002532:Intracranial Aneurysm / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009119:Muscle Contraction / Q000235:genetics*; D009130:Muscle, Smooth / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000099251:Myocardin
chemical_list: D000262:Adenylyl Cyclases; D005346:Fibroblast Growth Factors; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D064067:Rho Guanine Nucleotide Exchange Factors; D015534:Trans-Activators; D000099251:Myocardin; C577222:ARHGEF12 protein, human; C486356:FGF12 protein, human; C419510:adenylyl cyclase type V