MicroRNAs (miRNAs) were considered as powerful, post-transcriptional regulators in adipogenesis progress. However, the function of miR-141 was still unclear. Here, upregulation of miR-141 was found during adipocyte differentiation. In miR-141 transfected cells, triglyceride accumulation was increased, the adipogenesis related transcription factors and adipocyte markers levels of C/EBP alpha, PPAR gamma, and AP2 were up-regulated. Bioinformatic analyses and luciferase reporter assays were used to validate FOXA2 as a direct target gene of miR-141. By overexpressing miR-141, the expression of FOXA2 was remarkably repressed from both RNA and protein level. Using wildtype and mutant 3 '-UTR of the FOXA2, we identified the targeting sites for miR-141. The levels of c-myc and CCND1 were upregulated in miR-141 inhibitor group as well as the FOXA2 overexpression group, which indicated the Wnt/beta-catenin signaling was involved in the miR-141/FOXA2 cascade. Consistently, the expression of miR-141 was significantly increased in ob/ob, db/db, and diet-induced obese mice. Using miR-141 antagomir, the body weight, the white adipose tissue weight and the expression of C/EBP alpha, PPAR gamma, AP2 were reduced effectively. In conclusion, we demonstrated that miR-141 was a positive regulator of adipocyte differentiation through regulation of FOXA2.
[1]Tongji Univ, Sch Med, Shanghai East Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China.
[2]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China.
[3]Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Shanghai, Peoples R China.
[4]Tongji Univ, Sch Med, East Hosp, Dept Cardiothorac Surg, Cieme Rd 150 Pudong New Area, Shanghai 200120, Peoples R China.
(8.0+极速模式)