Diabetic Cardiomyopathy

NORAD[LncRNA]

miR-150-5p[miRNA]

ZEB1[mRNA]

HG-induced AC16 cells

Homo sapiens (human)

Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11259-11265. doi: 10.26355/eurrev_202011_23615.

NORAD regulates proliferation and apoptosis in cardiomyocytes under high-glucose treatment through miRNA-150-5p/ZEB1 axis.

qRT-PCR;

OBJECTIVE: The purpose of this study was to uncover the potential role of non-coding RNA activated by DNA damage (lncRNA NORAD) in the disease progression of diabetic cardiomyopathy (DCM) and the underlying mechanism. MATERIALS AND METHODS: Cell viability, 5-Ethynyl-2'-deoxyuridine (EdU)-positive ratio and apoptotic rate in human cardiomyocyte cell line AC16 undergoing treatment of normal-level (NG) or high-level glucose (HG) were assessed at first. NORAD level in HG-induced AC16 cells at different time points was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Subsequently, cell viability, EdU-positive ratio, and apoptotic rate in HG-induced AC16 cells overexpressing NORAD were evaluated. Next, subcellular distribution of NORAD was examined, and Dual-Luciferase reporter gene assay was performed to clarify the interaction among NORAD, miRNA-150-5p, and ZEB1. At last, rescue experiments were conducted to clarify the role of NORAD/miRNA-150-5p/ZEB1 axis in influencing the proliferation and apoptosis in HG-induced AC16 cells. RESULTS: Results revealed that HG treatment suppressed the proliferative ability and stimulated apoptosis in AC16 cells. Besides, NORAD was time-dependently downregulated in HG-induced AC16 cells, and it was mainly distributed in cytoplasm. In addition, the overexpression of NORAD enhanced proliferative ability, attenuated apoptosis, and increased Bcl-2/Bax ratio in HG-induced AC16 cells. Finally, NORAD/miRNA-150-5p/ZEB1 axis was verified to protect the malignant progression of DCM. CONCLUSIONS: NORAD is upregulated under high-level glucose treatment. Overexpression of NORAD protects DCM development via miRNA-150-5p/ZEB1 axis.