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Hypermethylation-mediated down-regulation of lncRNA TBX5-AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression.


ABSTRACT: 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.

SUBMITTER: Ma J 

PROVIDER: S-EPMC7294119 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Hypermethylation-mediated down-regulation of lncRNA TBX5-AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression.

Ma Jing J   Chen Shiyu S   Hao Lili L   Sheng Wei W   Chen WeiCheng W   Ma Xiaojing X   Zhang Bowen B   Ma Duan D   Huang Guoying G  

Journal of cellular and molecular medicine 20200505 11


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 fu  ...[more]

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