MALAT1 promoted cell proliferation and migration via MALAT1/miR‐155/MEF2A pathway in hypoxia of cardiac stem cells

Abstract

Accumulating evidence revealed that hypoxia contributed to many human diseases, including ischemic myocardium and heart failure (HF). In recent years, the roles of hypoxia in stem cell survival and cardiac biology have been studied extensively. However, the underlying molecular mechanisms remain to be elucidated. As a leading cause of HF, ischemic heart disease was correlated with hypoxia. In this study, we firstly constructed the hypoxia cell model by CoCl2 in cardiac stem cells (CSCs) and found that hypoxia induced the cell proliferation and migration potential in CSCs. Then, we demonstrated that the expression of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) was promoted in CoCl2‐induced CSCs hypoxia model. Furthermore, we found that knockdown of MALAT1 inhibited the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model. In addition, we revealed that MALAT1 regulated the microRNA‐155 (miR‐155) expression in CSCs under both the normal and hypoxia conditions and further, manipulation of the miR‐155 expression affected the role of MALAT1 in CoCl2‐induced CSCs hypoxia cell model. We then illustrated that miR‐155 regulated the myocyte enhancer factor 2A (MEF2A) expression in CSCs under both the normal and hypoxia conditions and further, changing the expression of MEF2A affected the role of miR‐155. Finally, we demonstrated that MALAT1 regulated the MEF2A expression and exerted its role via modulation of the MALAT1/miR‐155/MEF2A pathway. Taken together, our study illustrated that MALAT1 promoted the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model, acting mechanistically by promoting MEF2A expression via “sponging” miR‐155.

The role of lncRNA MALAT1 in cardiovascular disease

“…MALAT1 was initially identified in early‐stage non‐small cell lung cancer and profoundly induced by stimuli such as hypoxia, high glucose, cytokine and oxidative stress in ECs or cardiomyocytes . MALAT1 can regulate multiple pathophysiological processes such as proliferation, apoptosis, autophagy, and pyroptosis to participate in development of CVD …”

“…Proliferation and migration play an important role in angiogenesis or repair of CVD . MALAT1 was up‐regulated by hypoxia and could promote the proliferation and migration potential of cardiac stem cells (CSCs) and cardiac progenitor cells (CPCs) via sponging miR‐155 or miR‐125, respectively . However, inhibition of MALAT1 induced a characteristic phenotype switching from a proliferative toward a more migratory pattern loss in vascular smooth muscle cells (VSMCs) and lead to significant cell cycle arrest in the G2 phase .…”

“…Stem cells have great potential in cardiac regeneration and hold promising therapeutic effect for CVD . Hypoxia could promote the proliferation and migration of CSCs or CPCs accompanied by up‐regulation of MALAT1 . MALAT1 enhanced proliferation and migration potential of CSCs via sponging the miR‐155 targeting myocyte enhancer factor 2A .…”

“…Among them, metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is attracted more attention as it is profoundly expressed in ECs or cardiomyocytes under the conditions of hypoxia, high glucose, cytokines, and oxidative stress, which are the risk factors of CVD . Furthermore, MALAT1 was also found to regulate multiple pathophysiological processes such as proliferation, apoptosis, autophagy, and pyroptosis in ECs or cardiomyocytes …”

“…[8][9][10][11] Furthermore, MALAT1 was also found to regulate multiple pathophysiological processes such as proliferation, apoptosis, autophagy, and pyroptosis in ECs or cardiomyocytes. [8][9][10][11][12][13] In this review, we summarize recent progresses in research on molecular mechanism of MALAT1 on regulating the pathophysiological processes of CVD as well as its potential therapeutic applications.…”