Open Access
ARTICLE
miR-208a Promotes Apoptosis in H9c2 Cardiomyocytes by Targeting GATA4
Liying Gong1,2,3, Hongkun Jiang4, Guangrong Qiu1, Kailai Sun1,*
1
Department of Medical Genetics, School of Life Sciences, China Medical University, Shenyang, China
2
Department of Laboratory Medicine, The People’s Hospital of Liaoning Province, Shenyang, China
3
Department of Laboratory Medicine, The People’s Hospital of China Medical University, Shenyang, China
4
Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, China
* Corresponding Author: Kailai Sun. Email:
Congenital Heart Disease 2021, 16(5), 499-512. https://doi.org/10.32604/CHD.2021.015831
Received 19 January 2021; Accepted 26 February 2021; Issue published 03 June 2021
Abstract
Background: 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.
Material and Methods: 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
(Bcl)-2, an anti-apoptotic gene, was detected
by RT-qPCR, as well as
Gata4. After 48h overexpression of miR-208a,
GATA4 was detected via western blotting.
Dual luciferase reporting system was used to identify the binding sites of miR-208a to
Gata4.
Results: Expression
of miR-208a was upregulated in the CHD group via the control group (
p < 0.01). At P7, miR-208a had the highest
expression (p < 0.01), and which was highest in myocardiocytes via other organs or tissues (
p < 0.01) in adult rats.
The number of apoptotic cells increased significantly post-transfection with miR-208a (
p < 0.01), while decreased
with the miR-208a inhibitor via the control group (
p < 0.01). Compared with the control group, there was no
significant difference in the expression level of
Bcl-2 after miR-208a overexpression (
p > 0.05). The present study
proved that miR-208a binds directly to the 3´-UTR of
Gata4 at site 1,363-1,369 bp. Expression of
GATA4
decreased after miR-208a overexpression (
p < 0.01), but increased following transfection with a miR-208a inhibitor via the control group (
p < 0.05).
Conclusions: Our study demonstrated that miR-208a downregulates
Bcl-2
by directly targeting
GATA4, which may cause CHD. miR-208a may become a new biomarker or therapeutic target for CHD in the future.
Keywords
Cite This Article
Gong, L., Jiang, H., Qiu, G., Sun, K. (2021). miR-208a Promotes Apoptosis in H9c2 Cardiomyocytes by Targeting
GATA4.
Congenital Heart Disease, 16(5), 499–512. https://doi.org/10.32604/CHD.2021.015831