Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice

Abstract

Sox4 participates in the progression of embryo development and regulation of apoptosis in tumors. However, the effect and mechanism of Sox4 in myocardial infarction (MI) remains unclear. Therefore, we aimed at examining the role and molecular mechanism of Sox4 in the process of cardiomyocytes apoptosis during MI. The expression of Sox4 were obviously increased both in MI mice and in neonatal mouse cardiomyocytes treated with H 2 O 2. Overexpression of Sox4 promoted cardiomyocyte apoptosis with or without H 2 O 2 , whereas knocking down of Sox4 alleviated H 2 O 2-induced apoptosis in cardiomyocytes. Furthermore, silencing Sox4 by AAV-9 carried short hairpin RNA targeting Sox4 (AAV-9-sh-Sox4) markedly decreased cardiac infarct area, imprfoved cardiac dysfunction, and reversed apoptosis in MI mice. Mechanistically, there is a potential Sox4-binding site in the promoter region of Bim, and forced expression of Sox4 significantly promoted Bim expression in cultured cardiomyocytes with or without H 2 O 2 , whereas knocking down of Sox4 inhibited the expression of Bim. Further studies showed that silencing Bim attenuated Sox4-induced apoptosis in cardiomyocytes, indicating that Sox4 promoted cardiomyocytes apoptosis through regulation of Bim expression, which can be used as a potential therapeutic target for MI.

RETRACTED ARTICLE: Long non-coding RNA muscleblind like splicing regulator 1 antisense RNA 1 (LncRNA MBNL1-AS1) promotes the progression of acute myocardial infarction by regulating the microRNA-132-3p/SRY-related high-mobility-group box 4 (SOX4) axis

“…SOX4 has been found to increase myocardial cells apoptosis and is regarded as a promising target for treating AMI [ 27 ]. In our present study, SOX4 was discovered to be the target of miR-132-3p and bind to miR-132-3p depending on its 3ʹUTR according to the analysis of Targetscan database.…”

“…The labeled cells were regarded as apoptotic cells. Finally, the fluorescence microscope (Olympus, Japan) was used to take photograph of positive cells within six different random views [ 27 ].…”

“…miR-132-3p, located in chromosome 17p13.3, is identified to possess connections with multiple cancers including colorectal cancer, osteosarcoma, prostate cancer and gastric cancer [ 23 ]. Additionally, miR-132-3p is downregulated in myocardial infarction model and its upregulation effectively improves AMI [ 27 ]. Nevertheless, how miR-132-3p affects AMI is unclear now.…”

“…SRY-related high-mobility-group box 4 (SOX4) is a vital member of the SOX family that belongs to transcription factor and is involved in the development of embryo, cardiovascular and immune system [ 28 ]. Recent studies have shown that silencing SOX4 significantly reduced myocardial infarction size and apoptosis of myocardial cell in mice [ 27 ].…”

Circ_0124644 Serves as a ceRNA for miR-590-3p to Promote Hypoxia-Induced Cardiomyocytes Injury via Regulating SOX4

“…More and more studies have shown that SOX4 can participate in the development of malignant cancers such as breast cancer and gastric cancer by affecting cell growth, metastasis, and apoptosis (Ding et al, 2019;Song et al, 2019). A recent study showed that SOX4 expression was elevated in H 2 O 2 -induced cardiomyocytes, and its downregulation had a protective effect on cardiomyocytes injury (Zhang et al, 2021). Here, SOX4 was confirmed to be targeted by miR-590-3p.…”