Obesity-Induced miR-455 Upregulation Promotes Adaptive Pancreatic β-cell Proliferation Through the CPEB1/CDKN1B Pathway
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posted on 2022-01-14, 13:13 authored by Ada AdminAda Admin, Qianxing Hu, Jinming Mu, Yuhong Liu, Yue Yang, Yue Liu, Yi Pan, Yanfeng Zhang, Ling Li, Dechen Liu, Jianqiu Chen, Fangfang Zhang, Liang JinPancreatic β-cell adapt to compensate for increased metabolic demand
during obesity. Although the microRNA (miRNA) pathway has an essential
role in β-cell expansion, whether it is involved in adaptive
proliferation is largely unknown. First, we report that EGR2 binding to
the miR-455 promoter induced miR-455 upregulation in the pancreatic
islets of obesity mouse models. Then, in vitro gain- or loss-of-function
studies showed that miR-455 overexpression facilitated β-cell
proliferation. Knockdown of miR-455 in ob/ob mice via pancreatic
intraductal infusion prevented compensatory β-cell expansion.
Mechanistically, our results revealed that increased miR-455 expression
inhibits the expression of its target cytoplasmic polyadenylation
element binding protein 1 (CPEB1), an mRNA binding protein that plays an
important role in regulating insulin resistance and cell proliferation.
Decreased CPEB1 expression inhibits elongation of the poly-A tail and
the subsequent translation of Cdkn1b mRNA, reducing the CDKN1B
expression level and finally promoting β-cell proliferation. Taken
together, our results show that the miR-455/CPEB1/CDKN1B pathway
contributes to adaptive proliferation of β-cells to meet metabolic
demand during obesity.