Laboratory of Statistical Genetics and Epigenome, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
J Cell Physiol. 2022 Nov;237(11):4238-4250. doi: 10.1002/jcp.30872. Epub 2022 Sep 8.
The high level of progesterone and 17β-estradiol ratio (P4/E2) in follicular fluid has been considered as a biomarker of follicular atresia. CYP11A1, the crucial gene encoding the rate-limiting enzyme for steroid hormone synthesis, has been reported differently expressed in the ovary during follicular atresia. However, the regulation mechanism of CYP11A1 expression during follicular atresia still remains unclear. Here, we have demonstrated that lnc2300, a novel pig ovary-specific highly expressed cis-acting long noncoding RNA (lncRNA) transcribed from chromosome 7, has the ability to induce the expression of CYP11A1 and inhibit the apoptosis of porcine granulosa cells (GCs). Mechanistically, lnc2300, mainly located in the cytoplasm of porcine GCs, sponges and suppresses the expression of miR-365-3p through acting as a competing endogenous RNA (ceRNA), which further relieves the inhibitory effects of miR-365-3p on the expression of CYP11A1. Besides, CYP11A1 is validated as a direct functional target of miR-365-3p in porcine GCs. Functionally, lnc2300 is an antiapoptotic lncRNA that reduces porcine GC apoptosis by inhibiting the proapoptotic function of miR-365-3p. In summary, our findings reveal a cis-acting regulation mechanism of CYP11A1 through lncRNA, and define a novel signaling pathway, lnc2300/miR-365-3p/CYP11A1 axis, which is involved in the regulation of GC apoptosis and follicular atresia.
卵泡液中孕酮和 17β-雌二醇的高比值（P4/E2）被认为是卵泡闭锁的生物标志物。CYP11A1 是编码类固醇激素合成限速酶的关键基因，据报道在卵泡闭锁过程中在卵巢中表达不同。然而，CYP11A1 表达在卵泡闭锁过程中的调控机制仍不清楚。在这里，我们证明了 lnc2300，一种新型的猪卵巢特异性高表达顺式作用长非编码 RNA（lncRNA），由染色体 7 转录，具有诱导 CYP11A1 表达和抑制猪颗粒细胞（GCs）凋亡的能力。在机制上，lnc2300 主要位于猪 GCs 的细胞质中，通过作为竞争性内源性 RNA（ceRNA）来吸附和抑制 miR-365-3p 的表达，从而进一步解除 miR-365-3p 对 CYP11A1 表达的抑制作用。此外，CYP11A1 被验证为 miR-365-3p 在猪 GCs 中的直接功能靶标。功能上，lnc2300 是一种抗凋亡 lncRNA，通过抑制 miR-365-3p 的促凋亡功能减少猪 GC 凋亡。总之，我们的研究结果揭示了 CYP11A1 通过 lncRNA 的顺式作用调控机制，并定义了一个新的信号通路，lnc2300/miR-365-3p/CYP11A1 轴，参与 GC 凋亡和卵泡闭锁的调节。
