lncRNA FDNCR promotes apoptosis of granulosa cells by targeting the miR-543-3p/DCN/TGF-β signaling pathway in Hu sheep

Xiaolei Yao; XiaoXiao Gao; Yongjin Bao; M A El-Samahy; Jinyu Yang; Zhibo Wang; Xiaodan Li; Guomin Zhang; Yanli Zhang; Wujun Liu; Feng Wang

doi:10.1016/j.omtn.2021.02.030

lncRNA FDNCR promotes apoptosis of granulosa cells by targeting the miR-543-3p/DCN/TGF-β signaling pathway in Hu sheep

Mol Ther Nucleic Acids. 2021 Mar 1:24:223-240. doi: 10.1016/j.omtn.2021.02.030. eCollection 2021 Jun 4.

Authors

Xiaolei Yao^{1

2}, XiaoXiao Gao^{1

2}, Yongjin Bao^{1

2}, M A El-Samahy^{1

2}, Jinyu Yang³, Zhibo Wang^{1

2}, Xiaodan Li^{1

2}, Guomin Zhang^{1

2}, Yanli Zhang^{1

2}, Wujun Liu⁴, Feng Wang^{1

2}

Affiliations

¹ Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, China.
² Hu Sheep Academy, Nanjing Agricultural University, Nanjing 210095, China.
³ Biomarker Technologies Corporation, Beijing 101300, China.
⁴ College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.

Abstract

Long non-coding RNAs (lncRNAs) regulate the development of follicles and reproductive diseases, but the mechanisms by which lncRNAs regulate ovarian functions and fertility remain elusive. We profiled the expression of lncRNAs in ovarian tissues of Hu sheep with different prolificacy and identified 21,327 lncRNAs. Many of the lncRNAs were differentially expressed in different groups. We further characterized an lncRNA that was predominantly expressed in the ovaries of the low prolificacy Fec^B+ (LPB+) group and mainly present in granulosa cells (GCs), and the expression of this lncRNA decreased during follicular development, which we named follicular development-associated lncRNA (FDNCR). Next, we found that FDNCR directly binds miR-543-3p, and decorin (DCN) was identified as a target of miR-543-3p. FDNCR overexpression promoted GC apoptosis through increased expression of DCN, which could be attenuated by miR-543-3p. Furthermore, miR-543-3p increased and FDNCR reduced the expression of transforming growth factor-β (TGF-β) pathway-related genes, including TGF-β1 and inhibin beta A (INHBA), which were upregulated upon DCN silencing. Our results demonstrated that FDNCR sponges miR-543-3p in GCs and prevents miR-543-3p from binding to the DCN 3' UTR, resulting in DCN transactivation and TGF-β pathway inhibition and promotion of GC apoptosis in Hu sheep. These findings provide insights into the mechanisms underlying prolificacy in sheep.

Keywords: FDNCR; Hu sheep; apoptosis; granulosa cells; miR-543-3p.