Lnc-hipk1 inhibits mouse adipocyte apoptosis as a sponge of miR-497

Biofactors. 2021 Dec 2. doi: 10.1002/biof.1807. Online ahead of print.

Abstract

Noncoding RNAs (ncRNAs) such as microRNAs (miRNAs), long noncoding RNAs (lncRNA), and circular RNAs are closely related to the biological processes related to obesity. As a miRNA that widely present in different cell types, miR497 is proved to be involved in cell development. However, research on the role of miR-497 as a key factor in regulating the development of adipocytes is still in gap. The role of miR-497 in the apoptosis and proliferation of mouse-derived adipocytes was detected by RNA-seq analysis, RT-qPCR, Western blot, immunofluorescence, and dual-luciferase reporter assay. Using miR-497 mimics to treat 3T3-L1 cells, we found that miR-497 targeted Bcl-2 to promote adipocyte apoptosis through the mitochondrial pathway, and this effect was consistent in the apoptosis model composed of palmitic acid (PA) and hydrogen peroxide (H2 O2 ). LncRNA homeodomain-interacting protein kinase 1 (lnc-hipk1) sponged miR-148b to weaken its silencing of Bcl-2, forming the competitive endogenous RNAs (CeRNAs) regulatory network. Furthermore, overexpression of lnc-hipk1 inhibited the apoptosis of adipocytes by targeting miR-497/Bcl-2. Co-treatment of miR-497 and lnc-hipk1 showed that lnc-hipk1 reversed the apoptosis of adipocytes caused by miR-497 overexpression. And in vivo experiments further confirmed that this effect was also achieved by the CeRNA system of lnc-hipk1/miR-497/Bcl-2. In summary, lnc-hipk1 targets miR-497/Bcl-2 to regulate adipocyte apoptosis through the mitochondrial pathway. This research enriches the research content of ncRNAs and CeRNA in adipocyte development, and provides new targets for the treatment of obesity and other metabolic syndromes.

Keywords: CeRNA; adipocyte; apoptosis; lnc-hipk1; miR-497.