Yonsei Med J.  2020 Sep;61(9):780-788. 10.3349/ymj.2020.61.9.780.

MiR-542-5p Inhibits Hyperglycemia and Hyperlipoidemia by Targeting FOXO1 in the Liver

• Tian F
• Ying HM
• Wang YY
• Cheng BN
• Chen J

• KMID: 2505378
• DOI: http://doi.org/10.3349/ymj.2020.61.9.780

Abstract

Purpose
This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia.
Materials and Methods
An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1).
Results
MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primary hepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice.
Conclusion
Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.

Keyword

miR-542-5p; forkhead box O1; diabetes; hyperglycemia; hyperlipoidemia