miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.
AIM/INTRODUCTION
Obesity is considered an important risk factor for many metabolic disorders, especially type 2 diabetes mellitus, and microRNAs (miRNAs) play a vital role in the development of type 2 diabetes mellitus. Therefore, we conducted this study to investigate the role of miR-4431 in the obesity-associated pathobiology of type 2 diabetes mellitus.


MATERIALS AND METHODS
Subjects were divided into normal control (n = 36), obese (n = 36), and type 2 diabetes mellitus (n = 12) groups, and serum miR-4431 levels were analyzed. Adenovirus-vectored miR-4431 mimic or sponge was intraperitoneally injected into the normal diet group and the high-fat diet group (HFD) mice to investigate glucose tolerance, insulin sensitivity, and lipid levels. The downstream target genes of miR-4431 were predicted using bioinformatics, and they were verified in vitro.


RESULTS
Serum miR-4431 levels were significantly high in obese and type 2 diabetes mellitus individuals, and positively correlated with the body mass index and fasting plasma glucose levels. In HFD mice, miR-4431 levels in the serum, white adipose tissue, and liver were significantly increased. Moreover, miR-4431 impaired glucose tolerance, insulin sensitivity, and lipid metabolism in mice. Bioinformatic prediction suggested that TRIP10 and PRKD1 could be the downstream target genes of miR-4431. The HFD mice showed a remarkable reduction in the mRNA levels of TRIP10 and PRKD1 in the liver, which were countered by blocking miR-4431. In HepG2 and L02 cells, miR-4431 could downregulate TRIP10 and PRKD1 while blocking glucose uptake. The luciferase reporter assay showed that miR-4431 could bind TRIP10 and PRKD1 3'-UTR.


CONCLUSION
miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.
['Pan|Chongge|C|', 'Li|Menghuan|M|', 'Wang|Jingzhou|J|', 'Chu|Xiaolong|X|', 'Xiong|Jianyu|J|', 'Yang|Xin|X|', 'Tang|Yihan|Y|', 'Ma|Dingling|D|', 'Yuan|Chenggang|C|', 'Zhu|Jiaojiao|J|', 'Chang|Yongsheng|Y|', 'Zhang|Jun|J|https://orcid.org/0000-0001-9796-994X', 'Wang|Cuizhe|C|https://orcid.org/0000-0002-3338-9732']
miR-4431 Glucose metabolism Type 2 diabetes mellitus