Long non-coding RNA cytoskeleton regulator RNA (CYTOR) modulates pathological cardiac hypertrophy through miR-155-mediated IKKi signaling.
Pathological cardiac hypertrophy, which may lead to heart failure and sudden death, can be affected by multiple factors. In our previous study, we revealed that IKKi deficiency induced cardiac hypertrophy through the activation of the AKT and NF-kB signaling pathway in response to aortic banding (AB). Non-coding RNAs, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in normal developmental and pathological processes. In the present study, microarray analysis results from GEO database were analyzed, and upregulated lncRNAs in cardiac hypertrophy were identified. Of them, lncRNA cytoskeleton regulator RNA (CYTOR) obtained a fold-change of 6.16 and was positively correlated with IKBKE according to the data from The GTEx project. CYTOR knockdown significantly enhanced the inducible effect of AB operation on mice myocardial hypertrophy and Angiotensin II on cardiomyocyte hypertrophy. Moreover, miR-155 was significantly related to hypertrophic cardiomyopathy (HCM, |hsa05410) and predicted to target both CYTOR and IKBKE. Luciferase reporter and RIP assays revealed that CYTOR served as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE. Moreover, CYTOR knockdown reduced IKKi protein levels while activated NF-kB signaling pathway, whereas miR-155 inhibition exerted an opposing effect; the effect of CYTOR could be partially attenuated by miR-155 inhibition. Taken together, CYTOR might play a protective role in cardiac hypertrophy through miR-155 and downstream IKKi and NF-κB signaling, most possibly through serving as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE.
['Yuan|Yuan|Y|', 'Wang|Juan|J|', 'Chen|Qiuxiang|Q|', 'Wu|Qingqing|Q|', 'Deng|Wei|W|', 'Zhou|Heng|H|', 'Shen|Difei|D|']
D000818:Animals D001011:Aorta D001483:Base Sequence D006332:Cardiomegaly D002460:Cell Line D004195:Disease Models, Animal D020869:Gene Expression Profiling D005786:Gene Expression Regulation D017930:Genes, Reporter D006978:Hypertension, Renovascular D051550:I-kappa B Kinase D008156:Luciferases D008297:Male D051379:Mice D035683:MicroRNAs D032383:Myocytes, Cardiac D016328:NF-kappa B D062085:RNA, Long Noncoding D034741:RNA, Small Interfering D051381:Rats D017207:Rats, Sprague-Dawley D015398:Signal Transduction
Cardiac hypertrophy IKBKE miR-155 NF-κB signaling lncRNA CYTOR