Hypermethylation-mediated down-regulation of lncRNA TBX5-AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression
Hypermethylation-mediated down-regulation of lncRNA TBX5-AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression
复制标题
法洛四联症中高甲基化介导的 lncRNA TBX5-AS1:2 下调通过减少 TBX5 表达来抑制细胞增殖
DOI：
10.1111/jcmm.15298
复制
发表时间：
2020-05-05
影响因子：
5.3
通讯作者：
Huang, Guoying
中科院分区：
文献类型：
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作者：
Ma, Jing;Chen, Shiyu;Huang, Guoying
法洛四联症（Tetralogy of Fallot，TOF）是最常见的复杂先天性心脏病（Complex Congenital Heart Disease，CHD），病因不明.虽然长链非编码RNA（lncRNA）与心脏发育和几种CHD有关，但它们在TOF中的作用尚不清楚。本研究旨在研究失调的lncRNA如何促进TOF。通过基因表达数据挖掘、生物信息学分析和临床心脏组织样本检测，我们发现了一个新的功能未知的反义lncRNA TBX 5-AS 1：2，它在TOF患者的损伤心脏组织中显著下调。LncRNA TBX 5-AS 1：2主要定位于人胚肾293（HEK 293 T）细胞核内，与心脏发育的重要调控因子T-box转录因子5（TBX 5）的正义mRNA重叠区形成RNA-RNA双链结构。通过启动子超甲基化敲低lncRNA TBX 5-AS 1：2通过RNA-RNA相互作用影响其mRNA稳定性，从而在mRNA和蛋白质水平降低TBX 5表达。此外，lncRNA TBX 5-AS 1：2敲低抑制HEK 293 T细胞的增殖。总之，这些结果表明lncRNA TBX 5-AS 1：2可能通过靶向TBX 5影响细胞增殖而参与TOF。
Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) with uncertain cause. Although long non-coding RNAs (lncRNAs) have been implicated in heart development and several CHDs, their role in TOF is not well understood. This study aimed to investigate how dysregulated lncRNAs contribute to TOF. Using Gene Expression Omnibus data mining, bioinformatics analysis and clinical heart tissue sample detecting, we identified a novel antisense lncRNA TBX5-AS1:2 with unknown function that was significantly down-regulated in injured cardiac tissues from TOF patients. LncRNA TBX5-AS1:2 was mainly located in the nucleus of the human embryonic kidney 293 (HEK293T) cells and formed an RNA-RNA double-stranded structure in the overlapping region with its sense mRNA T-box transcription factor 5 (TBX5), which is an important regulator in heart development. Knock-down of lncRNA TBX5-AS1:2 via promoter hypermethylation reduced TBX5 expression at both the mRNA and protein levels by affecting its mRNA stability through RNA-RNA interaction. Moreover, lncRNA TBX5-AS1:2 knock-down inhibited the proliferation of HEK293T cells. In conclusion, these results indicated that lncRNA TBX5-AS1:2 may be involved in TOF by affecting cell proliferation by targeting TBX5.