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Biomed Pharmacother. 2018 Oct;106:1751-1759. doi: 10.1016/j.biopha.2018.07.141. Epub 2018 Jul 31.

miR-208b targets Bax to protect H9c2 cells against hypoxia-induced apoptosis.

Author information

1
Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao, China.
2
Department of Ultrasound, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China.
3
Department of Ultrasound, The Affiliated Hospital of Jining Medical College, Jining, China.
4
Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: qddx1016sunyue@126.com.

Abstract

BACKGROUND:

miR-208 family members have been considered as promising biomarkers in myocardial infarction (MI). Among which, miR-208a and miR-499 are reported to function as ischemic injury promoting miRNAs. This study aimed to explore the in vitro function of miR-208b in MI, which has not been widely studied.

METHODS:

RT-qPCR was conducted to measure the expression changes of miR-208b in MI patients, MI mouse model and H9c2 cells stimulated by hypoxia. H9c2 cells were subjected to hypoxia before which miR-208b expression was altered by transfection. CCK-8, flow cytometry and Western blot were performed to detect cell survival. Besides, the regulatory relationship between miR-208b, Bax, and PI3K/AKT was tested by luciferase reporter, RT-qPCR and Western blot.

RESULTS:

Serum levels of miR-208b in MI patients were significantly higher than those in the healthy controls. Also, miR-208b was up-regulated in mouse model and cell model of MI. Overexpression of miR-208b protected H9c2 cells against hypoxia-induced apoptosis, as the viability was increased, apoptosis rate was decreased, Bax and Cytochrome c were down-regulated, and Bcl-2 was up-regulated. Bax was a target gene of miR-208b. And miR-208b could not protect H9c2 cells when Bax was overexpressed. More interestingly, miR-208b activated PI3K/AKT pathway via targeting Bax, and the activated PI3K/AKT pathway could further repress Bax expression. Finally, blocking PI3K/AKT pathway by using LY294002 eliminated the myocardioprotective effects of miR-208b.

CONCLUSION:

miR-208b is highly expressed during MI, and miR-208b protects H9c2 cells against hypoxia-induced apoptosis. miR-208b exerts myocardioprotective effect via targeting Bax and activating PI3K/AKT pathway.

KEYWORDS:

Bax; H9c2 cell; Hypoxia; Myocardial infarction; PI3K/AKT pathway; miR-208b

PMID:
30119250
DOI:
10.1016/j.biopha.2018.07.141
[Indexed for MEDLINE]

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