The let-7g microRNA promotes follicular granulosa cell apoptosis by targeting transforming growth factor-β type 1 receptor

• 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.

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.