miR-1306 Mediates the Feedback Regulation of the TGF-ß/SMAD Signaling Pathway in Granulosa Cells

Yang, Liu; Du, Xing; Liu, Lu; Cao, Qiuyu; Pan, Zengxiang; Li, Qifa

TGFBR2 is known to be the first receptor to be activated in the classical TGF-β/SMAD signaling pathway and it mediates the effects of TGF-β ligands (TGF-β1) by forming a receptor-receptor complex with TGFBR1, also named ALK5. Actually, ALK1 could also act as partner of TGFBR2 [25] but ALK1 mediates the phosphorylation of SMAD1/5/8 [26] and activates SMAD2/3 only in the presence of ALK5, which is essential for SMAD2/3 phosphorylation [27] . In this study, we identified and characterized the 3'-UTR of porcine TGFBR2 gene and observed several response elements such as ARE, GREs, and MREs for the first time. It is well known that the levels of mRNAs are largely controlled by mRNA decay mechanisms including mRNA decay induced or inhibited proteins and small regulatory RNAs [28, 29] . Furthermore, some cis-elements in the mRNAs 3'-UTRs are also known to mediate the regulation of mRNA decay, such as PAT [29, 30] , ARE [31] , iron-responsive element (IRE) [32] , GRE [33] , and MRE [34] . Many studies have demonstrated that the expression of TGFBR2 is modulated by MREs and their miRNAs in various cell types, such as miR-145 in vascular smooth muscle cells [35] , miR-9-5p in hepatic stellate cells [36] , miR-9 and miR-9-5p fibroblasts (HCFs) [6, 37] , miR-520e, miR-9-5p, and miR-135b in cancer cells [38] [39] [40] . Notably, miR-143 [23] , miR-