Abstract：
In bovine follicular development, the proliferation of bovine granulosa cells affects follicular selection, atresia, and cystic follicle formation. When cystic follicles appear on the ovaries, granulosa cells stop proliferating, resulting in the reduction of granulosa cells layer. In our previous study, the whole transcriptome sequencing revealed that Bone morphogenetic protein receptor 2 (BMPR2) was differentially expressed between cystic and normal follicular granulosa cells. We speculated that long noncoding RNA may act as competing endogenous RNA targeting microRNAs and then regulating the expression of BMPR2 and the function of granulosa cells, thereby affecting follicular development and cyst formation. In this study, the results elucidated that long noncoding RNA S100PBP (NONBTAT011846.2) directly bound miR-2285bc, which targeted in the BMPR2 3\'-UTR. miR-2285bc suppresses granulosa cells proliferation by downregulating BMPR2 expression. Furthermore, long noncoding RNA S100PBP was silenced by small interfering RNA, and long noncoding RNA S100PBP regulated BMPR2 expression by sponging miR-2285bc investigated through cross-verification. When small interfering RNA of long noncoding RNA S100PBP was transfected into granulosa cells, the results revealed similar molecular changes as those transfected with miR-2285bc mimics. Silencing long noncoding RNA S100PBP or overexpressing miR-2285bc altered the expressions of some follicular development-related genes, which could be related to follicular cyst occurrence. In conclusion, our findings support that long noncoding RNA S100PBP regulates the expression of BMPR2 through sponge miR-2285bc, promotes the proliferation of granulosa cells, inhibits their apoptosis, and increases the synthesis and secretion of follicular steroid hormones, thus promoting the development of bovine follicles.
摘要：
在牛卵泡发育中，牛颗粒细胞的增殖影响卵泡的选择，闭锁,和囊性卵泡形成。当卵巢出现囊性卵泡时，颗粒细胞停止增殖,导致颗粒细胞层减少。在我们之前的研究中,全转录组测序显示，骨形态发生蛋白受体2（BMPR2）在囊性和正常卵泡颗粒细胞中差异表达。我们推测长链非编码RNA可能作为靶向microRNAs的竞争性内源性RNA，进而调节BMPR2的表达和颗粒细胞的功能，从而影响卵泡发育和囊肿形成。在这项研究中,结果阐明长链非编码RNAS100PBP（NONBTAT011846.2）直接结合miR-2285bc，以BMPR23'-UTR为目标。miR-2285bc通过下调BMPR2表达抑制颗粒细胞增殖.此外，长链非编码RNAS100PBP被小干扰RNA沉默，和长链非编码RNAS100PBP通过交叉验证研究的miR-2285bc来调节BMPR2的表达。当长非编码RNAS100PBP的小干扰RNA转染颗粒细胞时，结果显示与miR-2285bc模拟物转染的分子变化相似.沉默长链非编码RNAS100PBP或过表达miR-2285bc改变了一些卵泡发育相关基因的表达,这可能与卵泡囊肿的发生有关。总之,我们的研究结果支持长链非编码RNAS100PBP通过海绵miR-2285bc调节BMPR2的表达，促进颗粒细胞的增殖，抑制它们的凋亡，并增加卵泡类固醇激素的合成和分泌，从而促进牛卵泡的发育。
