The let-7g microRNA promotes follicular granulosa cell apoptosis by targeting transforming growth factor-β type 1 receptor. (5th July 2015)

• Record Type: Journal Article
• Authors: Zhou, Jilong; Liu, Jiying; Pan, Zengxiang; Du, Xing; Li, Xinyu; Ma, Baiquan; Yao, Wang; Li, Qifa; Liu, Honglin
• Is Part Of: Molecular and cellular endocrinology. Volume 409(2015)
• Page Start: 103
• Page End: 112
• Publication Date: 2015-07-05
• Subjects: Pig -- let-7g -- Granulosa cell apoptosis -- Follicular atresia -- Transforming growth factor-β type 1 receptor; FACS fluorescence-activated cell sorting -- GC granulosa cell -- miRNA microRNA -- NC negative control -- p-SMAD3 phosphorylated SMAD3 -- siRNA small interfering RNA -- TGFBR1 transforming growth factor-β type 1 receptor -- UTR untranslated region; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.03.012
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Let-7g promotes porcine granulosa cell apoptosis. TGFBR1 is a validated target of let-7g in granulosa cells. Let-7g regulates cell apoptosis by targeting TGFBR1 and down-regulating TGF-β pathway. Knockdown of TGFBR1 can suppress the inhibition function of let-7g inhibitor on GC apoptosis. 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.