Inhibition of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 attenuates high glucose-induced cardiomyocyte apoptosis via regulation of miR-181a-5p

Abstract

Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific shorthairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.

Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1

“…We first found that LPS could induce upregulation of miR‐181a, and LPS‐induced inflammation could be attenuated by the inhibition of miR‐181a. In addition, miR‐181a can promote several cell apoptosis, such as follicular granulosa cell, 17 cardiomyocyte, 18 cortical neurons 19 . We also found that miR‐181a could promote the apoptosis of mouse peritoneal macrophage.…”

Long non-coding RNA LUCAT1 inhibits myocardial oxidative stress and apoptosis after myocardial infarction via targeting microRNA-181a-5p

“…In the acute cellular rejection of heart transplantation, the expression of miR-181a-5p is obviously elevated [ 35 ]. Moreover, miR-181a-5p plays an essential role in the regulation of high glucose-managed cardiomyocytes [ 36 ]. Our exploration demonstrated that the miR-181a-5p has reduced expression in the H 2 O 2 -steered cells.…”

Long Non-coding RNA: A Key Regulator in the Pathogenesis of Diabetic Cardiomyopathy

“…Thus, melatonin exerts its antifibrotic function caused by its ability to inhibit lncR-MALAT1/miR-141 pathway in DM mice (24). In another study, Cheng et al (43) demonstrated that MALAT1 expression is upregulated in the myocardium in DCM mice, and knockdown of MALAT1 obviously alleviates hyperglycemia induced cardiomyocyte apoptosis through releasing miR-181a-5p and regulating the p53-p21 pathway. Furthermore, a recent study presents that si-MALAT1 alleviates collagen accumulation and inflammation in hyperglycemia cardiac fibroblasts and DCM mice via the Hippo-YAP pathway and CREB (44).…”