LncRNA-uc.167 influences cell proliferation, apoptosis and differentiation of P19 cells by regulating Mef2c.
In our previous study we screened thousands of lncRNAs for their relationship with ventricular septal defect. Among these lncRNAs, uc.167 attracted our attention for its high level of conservation and that it was antisense to the Mef2c gene, which encodes myocyte enhancer factor 2C. This study aims to investigate the role of uc.167 during cardiomyocyte maturation in P19 cells induction and possible mechanism. The uc.167 expression level in human heart tissue of ventricular septum defect (VSD) was evaluated by qRT-PCR. The UCSC database was searched to investigate the bioinformatics of uc.167. We constructed overexpression vector of uc.167 and Mef2c. To detect proliferation and apoptosis, we combined cell cycle analysis and CCK8, Hoechst staining, flow cytometry and caspase-3 assays, respectively. The cardiomyogenesis related RNAs (cTnT, GATA4, and Mef2c) and proteins were detected by qRT-PCR and Western blotting. In this study, we found that uc.167 expression was significantly increased in VSD heart tissues. uc.167 is on the opposite strand to the coding gene Mef2c. The expression model of Mef2c and uc.167 showed an opposite correlation in the embryonic development and process of differentiation of P19 cells into cardiomyocytes. Overexpression of uc.167 inhibited proliferation but promoted apoptosis in P19 cells compared with the vector group, and those relative mRNAs and proteins decreased during the differentiation process. Whereas, co-expression of Mef2c and uc.167 can partially reverse the negative effects of uc.167 on proliferation, apoptosis and differentiation. Taken together, our findings suggest that uc.167 contributes to the development potential of VSD and may constitute a potential therapeutic target in this disease. uc.167 influences cell proliferation, apoptosis and differentiation of P19 cell by regulating Mef2c.
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China.
Guixian
G
Song
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China.
Yahui
Y
Shen
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China.
Zhongbao
Z
Ruan
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Xing
X
Li
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yumei
Y
Chen
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China.
Wei
W
Yuan
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China.
Xiangwei
X
Ding
Department of Cardiology, Taizhou People's Hospital, Taizhou 225300, China. Electronic address: tzheart@126.com.
Li
L
Zhu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: lmqian@njmu.edu.cn.
Lingmei
L
Qian
D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D005333:Fetus; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006345:Heart Septal Defects, Ventricular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D062085:RNA, Long Noncoding
Heart development; Mef2c; P19 cells; uc.167