title: The let-7g microRNA promotes follicular granulosa cell apoptosis by targeting transforming growth factor-β type 1 receptor.
abstract: The intronic microRNA let-7g controls cell differentiation and proliferation during angiogenesis and oncogenesis. Here, we demonstrate that let-7g regulates granulosa cell (GC) apoptosis and follicular atresia in the pig ovary. Bioinformatics analyses and luciferase reporter assays showed that transforming growth factor-β type 1 receptor (TGFBR1) is a let-7g target. Overexpression of let-7g induced apoptosis of porcine GCs in vitro and repressed the mRNA and protein levels of TGFBR1, as well as the level of phosphorylated SMAD3 (p-SMAD3) protein. RNA interference-mediated knockdown of TGFBR1 and inhibitor LY2157299-mediated blocking of TGFBR1 significantly increased the rate of apoptosis of GCs and Caspase-3 activity. In addition, treatment of porcine GCs with TGF-β1 reduced the level of let-7g and increased the levels of the TGFBR1 mRNA and proteins significantly. Overall, these results demonstrate that let-7g regulates the apoptosis of GCs in the pig ovary by targeting TGFBR1 and down-regulating the TGF-β signaling pathway.
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Jilong
authors: J
authors: Zhou
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Jiying
authors: J
authors: Liu
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Zengxiang
authors: Z
authors: Pan
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Xing
authors: X
authors: Du
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Xinyu
authors: X
authors: Li
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Baiquan
authors: B
authors: Ma
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors: Wang
authors: W
authors: Yao
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: liqifa@njau.edu.cn.
authors: Qifa
authors: Q
authors: Li
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: liuhonglin@njau.edu.cn.
authors: Honglin
authors: H
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D011720:Pyrazoles; D011804:Quinolines; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C557799:LY-2157299
keywords: Follicular atresia; Granulosa cell apoptosis; Pig; Transforming growth factor-β type 1 receptor; let-7g