LncRNA-066/236簇介导TGF-β信号通路调控猪卵泡颗粒细胞中Wnt信号通路分子机制的探究

TGF-β信号通路是影响母猪繁殖性能、卵泡闭锁与颗粒细胞凋亡的关键信号通路。申请人前期研究发现敲减TGF-β通路核心成员SMAD4可抑制猪卵泡颗粒细胞中Wnt信号通路关键受体FZD4的表达，但机制尚不清楚。依赖SMAD4的lncRNA-miRNA-mRNA互作网络显示lncRNA-066/236簇可与miR-29c、FZD4形成调控通路，并证实此通路参与调控猪卵泡颗粒细胞凋亡。因此，我们猜想TGF-β信号通路可能通过上述调控轴影响Wnt信号通路，进而调控猪卵泡颗粒细胞凋亡。为了验证此假设，本项目拟分析SMAD4-lncRNA-066/236簇轴、lncRNA-066/236簇-miR-29c轴、miR-29c-FZD4轴的形成与互作机制，解析TGF-β信号通路通过lncRNA-066/236簇调控Wnt信号通路的机制，为揭示TGF-β通路调控猪卵泡闭锁的机制、提高母猪繁殖力提供依据。

TGF-β signaling pathway has been proved to play a critical role in regulating sow reproductive performance, follicular atresia and granulosa cell (GC) apoptosis. After preliminary study, applicant found that abrogation of SMAD4, the core member of TGF-β signaling pathway, could suppress the expression of FZD4 which is a important receptor of Wnt signaling pathway in porcine GCs with an unknown mechanism. SMAD4-dependent lncRNA-miRNA-mRNA interaction network was built and showed that lncRNA-066/236 cluster with miR-29c and FZD4 could form a regulatory pathway which was further proved to be involved in regulating porcine GC apoptosis. Based on these findings, we speculate that TGF-β signaling pathway regulates Wnt signaling pathway through lncRNA-066/236 cluster-miR-29c-FZD4 axis and affects porcine GC apoptosis. To address this, the project aims to investigate the formation mechanism of SMAD4-lncRNA-066/236 cluster axis, lncRNA-066/236 cluster-miR-29c axis and miR-29c-FZD4 axis and analyze the mechanism for lncRNA-066/236 cluster mediates TGF-β signaling pathway regulation to Wnt signaling pathway. This study will provide a theoretical basis for revealing the mechanism of TGF-β signaling pathway modulating follicular atresia and improving sow fertility.