Sp1-induced LncRNA CTBP1-AS2 is a novel regulator in cardiomyocyte hypertrophy by interacting with FUS to stabilize TLR4.
Cardiovasc Pathol. 2019 May 07;42:21-29
Authors: Luo X, He S, Hu Y, Liu J, Chen X
Cardiomyocyte hypertrophy is a heart response adapting to increasing cardiac load. Prolonged cardiomyocyte hypertrophy indicates a higher risk of heart failure or even cardiac death. Long noncoding RNAs have been largely reported to modulate human diseases. CTPB1-AS2 is a newly discovered lncRNA reported as an oncogene in papillary thyroid cancer, but its function in cardiomyocyte hypertrophy has never been probed. Toll-like receptor 4 (TLR4) is recognized to play important roles in cardiomyocyte hypertrophy. The present study aimed to investigate the role of CTBP1-AS2 in cardiomyocyte hypertrophy. First, we discovered the low expression of CTBP1-AS2 in normal heart tissues in GETx database. Then, we established cardiomyocyte hypertrophy models on mice and cardiomyocytes through transverse aortic constriction surgery and Ang II treatment. We revealed the up-regulation of CTBP1-AS2 and TLR4 in cardiomyocyte hypertrophy models. Also, we confirmed the positive correlation between CTBP1-AS2 and TLR4 expressions in cardiomyocyte hypertrophy tissues. Loss-of-function assays confirmed that inhibiting CTBP1-AS2 attenuated the Ang II-induced cardiomyocyte hypertrophy. Mechanism research showed that CTBP1-AS2 stabilized TLR4 mRNA by recruiting FUS. Rescue assays certified that CTBP1-AS2 regulated cardiomyocyte hypertrophy through TLR4. Finally, we found Sp1 as an upstream activator for CTBP1-AS2 expression. In conclusion, our study uncovered CTBP1-AS2 as a novel regulator of cardiomyocyte hypertrophy through regulating TLR4, providing a new potential treatment target for cardiomyocyte hypertrophy.
PMID: 31220774 [PubMed – as supplied by publisher]