miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling.
MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein α (Cebpa), peroxisome proliferator-activated receptor γ (Pparg), adipocyte fatty acid binding protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential transcriptional regulators of preadipocyte differentiation and lipid storage in mature adipocytes. Canonical Wnt/β-catenin signaling is recognized as a negative molecular switch during adipogenesis. In the present work we found that miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-135a-5p impairs the expressions of adipogenic marker genes as well as lipid droplet accumulation and triglyceride content, indicating the importance of miR-135a-5p for adipogenic differentiation and adipogenesis. Further studies show that miR-135a-5p directly targets adenomatous polyposis coli (Apc), contributes to the translocation of β-catenin from cytoplasm to nucleus, and then activates the expressions of cyclin D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/β-catenin signaling. In addition, inhibition of APC with siRNA exhibits the same effects as overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/β-catenin signaling by directly targeting Apc. Taken together, these results offer profound insights into the adipogenesis mechanism and the development of adipose tissue.
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaKey Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Chen
C
Chen
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Yongdong
Y
Peng
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Yinglin
Y
Peng
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China pjhzau@163.com jswhzau@163.com.
Jian
J
Peng
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of ChinaHunan Institute of Animal and Veterinary ScienceChangsha 410131, People's Republic of ChinaDepartment of Animal Nutrition and Feed ScienceCollege of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China pjhzau@163.com jswhzau@163.com.
Siwen
S
Jiang
D041721:3T3-L1 Cells; D021581:Active Transport, Cell Nucleus; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D002460:Cell Line; D006224:Cricetinae; D019938:Cyclin D1 / Q000096:biosynthesis; D064429:Fatty Acid Synthases / Q000009:adverse effects; D050556:Fatty Acid-Binding Proteins / Q000009:adverse effects; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C530105:Ccnd1 protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; C489428:Myc protein, mouse; D047495:PPAR gamma; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D064429:Fatty Acid Synthases
3T3-L1 preadipocyte differentiation; APC; Wnt/β-catenin; adipogenesis; miR-135a-5p