Long non-coding RNA AW112010 improves insulin resistance in adipocytes of aging mice through the miR-204/POU2F2 axis
10.3760/cma.j.cn311282-20230316-00116
- VernacularTitle:长链非编码RNA AW112010通过miR-204/POU2F2轴改善衰老小鼠脂肪细胞的胰岛素抵抗
- Author:
Rui WANG
1
;
Shuwen WANG
;
Yifan ZHANG
;
Yaqi HU
;
Qi YUAN
;
Yuan WEN
;
Xiaoling CHEN
;
Ting LU
;
Ying ZHENG
;
Zhiyong LIN
;
Mengzhen XUE
;
Yaqi WANG
;
Fangqi XIA
;
Leiqi ZHU
;
Chengfu YUAN
Author Information
1. 三峡大学，基础医学院，国家中医药管理局中药药理（肿瘤）科研三级实验室，宜昌 443002
- Keywords:
Aging;
LncRNA AW112010;
miR-204-5p;
POU2F2;
Insulin resistance
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(1):44-52
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.
