Long non-coding RNA DANCR alleviates hypoxia-caused H9c2 cells damage through up regulation of HIF-1α

Abstract

Hypoxia is an important cause of myocardial cell loss, further inducing various heart illnesses, including acute myocardial infraction (AMI). Long non-coding RNA (LncRNA) discrimination antagonising non-protein coding RNA (DANCR) was firstly identified as epidermal cell differentiation suppressor. Here, we aimed to explore the effects and mechanism of DNACR in hypoxia-induced H9c2 cells. Hypoxic cells were made through 94% N 2 , 5% CO 2 , and 1% O 2 environment for 24 h. Cell viability and apoptosis were detected via methyl thiazolyl tetrazolium (MTT) method and flow cytometry analysis, respectively. The expression of DANCR and HIF-1a was examined via qRT-PCR. The expression of proteins related to cell apoptosis and PI3K/AKT/mTOR and ERK1/2 signal pathways was examined through western blot analysis. We found that hypoxia induced obvious cell activity inhibition and apoptosis increasing in H9c2 cells. DANCR was negatively regulated under hypoxia condition. Overexpression of DANCR rescued activity and attenuated apoptosis. Moreover, the overexpression of DANCR elevated the activation of PI3K/AKT/mTOR and ERK1/2 pathways. Further study indicated that DANCR could up-regulate the expression of HIF-1a. Si-HIF-1a transfection could remove the beneficial effects of DANCR overexpression in hypoxia-caused H9c2 cells damage. In conclusion, DANCR alleviated hypoxia-caused H9c2 cells damage through positive regulation of HIF-1a.GRAPHICAL ABSTRACT ARTICLE HISTORY

Overexpression of lncRNA Dancr inhibits apoptosis and enhances autophagy to protect cardiomyocytes from endoplasmic reticulum stress injury via sponging microRNA-6324

“…lncRNA Dancr has been reported to protect H9c2 cardiomyocytes against hypoxia-induced damage (18). The present study indicated that Dancr protected H9C2 cells against Figure 6.…”

“…Further investigation revealed that Dancr functions as an oncogene in various types of cancer, including hepatocellular carcinoma (14), non-small cell lung carcinoma (15,16) and osteosarcoma (17). Recently, Dancr has been reported to alleviate hypoxia-induced H9c2 cardiomyocyte damage by upregulating hypoxia inducible factor-1α (18). In addition, Dancr decreased hypoxia-and hypoglycemia-induced damage of cerebral microvascular endothelial cells via regulating miR-33a-5p/spliced X-box-binding protein 1 (Xbp1s) (19).…”

Signaling pathways and targeted therapy for myocardial infarction

“…LncRNA UCA1 relieves cardiomyocytes via declining miR-122 and activating the Akt/ mTOR pathway 86 . Likewise, studies illustrate that lncRNA UCA1 and DANCR are cardioprotective by decreasing miRNAmediated mTOR signaling 86,87 .…”

Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis

“…Specifically, the corresponding protein was separated with 7.5 and 10% SDS-PAGE and transferred to polyvinylidene difluoride membranes. Afterward, the membranes were blocked with 5% skim milk for 2 h in room temperature (Qiu et al, 2020). They were incubated with primary antibodies against GAPDH (Proteintech, Wuhan, China); Tet1 (Signalway Antibody, College Park, MD); Hadh (Signalway Antibody, College Park, MD); Kcnn1 (Signalway Antibody, College Park, MD); Caspase3 (Proteintech, Wuhan, China); and Cleavd-caspase3 (Cell Signaling Technology, Danvers, MA); bcl-2 (Abcam, Cambridge, MA); Bax (Abcam, Cambridge, MA); HIF-1α (Abcam, Cambridge, MA); and Mettl3 (Proteintech, Wuhan, China) overnight at 4 °C.…”