Protective effect of lncRNA CRNDE on myocardial cell apoptosis in heart failure by regulating HMGB1 cytoplasm translocation through PARP-1

Arch Pharm Res. 2020 Dec;43(12):1325-1334. doi: 10.1007/s12272-020-01290-7. Epub 2020 Nov 29.

Abstract

Long non-coding RNAs (lncRNAs) are bound up with the regulation of various diseases. Here, we probed into the effect of lncRNA colorectal neoplasia differentially expressed (CRNDE) on heart failure (HF). The pathological alterations and cell apoptosis of heart tissues were observed by hematoxylin-eosin and TUNEL staining. The viability or apoptosis of mouse myocardial cells HL-1 was tested by XTT or flow cytometry. The interaction between lncRNA CRNDE and poly-ADP-ribose polymerase 1 (PARP-1) was verified by RNA immunoprecipitation and RNA pull-down. The stability of the PARP-1 protein and the acetylation level of high mobility group box-1 (HMGB1) were determined by cycloheximide-chase and immunoprecipitation, respectively. LncRNA CRNDE expression was decreased in HF mice tissues and doxorubicin (Dox)-treated HL-1 cells, whereas PARP-1 and HMGB1 were increased. The overexpression of lncRNA CRNDE restrained HL-1 cell apoptosis induced by Dox. Moreover, the interaction between CRNDE and PARP-1 was corroborated, CRNDE negatively regulated PARP-1 expression, and the overexpression of CRNDE reduced PARP-1 protein stability. In HL-1 cells, PARP-1 positively regulated the acetylation level and cytoplasm translocation of HMGB1. CRNDE restrained Dox-induced apoptosis in mouse myocardial cells via the PARP-1/HMGB1 pathway.

Keywords: HF; HMGB1; LncRNA CRNDE; Myocardial cell; PARP-1.