@Article{CHD.2021.015831,
AUTHOR = {Liying Gong, Hongkun Jiang, Guangrong Qiu, Kailai Sun},
TITLE = {miR-208a Promotes Apoptosis in H9c2 Cardiomyocytes by Targeting <i>GATA4</i>},
JOURNAL = {Structural and Congenital Heart Disease},
VOLUME = {16},
YEAR = {2021},
NUMBER = {5},
PAGES = {499--512},
URL = {http://www.techscience.com/schd/v16n5/42683},
ISSN = {3071-1738},
ABSTRACT = {<b>Background:</b> microRNAs are crucial for cardiovascular development and are associated with congenital heart disease (CHD). Recent studies have shown that microRNAs play a role in heart development and is closely related to
CHD. The present study investigated the underlying mechanism of microRNA-208a (miR-208a) in “simple”
CHD. <b>Material and Methods:</b> Reverse transcription-quantitative PCR (RT-qPCR) demonstrated miR-208a
expression levels in children with CHD (n = 27) compared with normal controls (n = 29), in cardiomyocytes from
embryo 10 (E10) to post-birth (P7) and organs in adult rats in healthy rats. Apoptosis of H9c2 cells after transfection with miR-208a detected by TUNEL assay. B-cell lymphoma <i>(Bcl)-2</i>, an anti-apoptotic gene, was detected
by RT-qPCR, as well as <i>Gata4</i>. After 48h overexpression of miR-208a, <i>GATA4</i> was detected via western blotting.
Dual luciferase reporting system was used to identify the binding sites of miR-208a to <i>Gata4</i>. <b>Results: </b>Expression
of miR-208a was upregulated in the CHD group via the control group (<i>p</i> < 0.01). At P7, miR-208a had the highest
expression (p < 0.01), and which was highest in myocardiocytes via other organs or tissues (<i>p</i> < 0.01) in adult rats.
The number of apoptotic cells increased significantly post-transfection with miR-208a (<i>p</i> < 0.01), while decreased
with the miR-208a inhibitor via the control group (<i>p</i> < 0.01). Compared with the control group, there was no
significant difference in the expression level of <i>Bcl-2</i> after miR-208a overexpression (<i>p</i> > 0.05). The present study
proved that miR-208a binds directly to the 3´-UTR of <i>Gata4</i> at site 1,363-1,369 bp. Expression of <i>GATA4</i>
decreased after miR-208a overexpression (<i>p</i> < 0.01), but increased following transfection with a miR-208a inhibitor via the control group (<i>p</i> < 0.05). <b>Conclusions:</b> Our study demonstrated that miR-208a downregulates <i>Bcl-2</i>
by directly targeting <i>GATA4</i>, which may cause CHD. miR-208a may become a new biomarker or therapeutic target for CHD in the future.},
DOI = {10.32604/CHD.2021.015831}
}