Department of Obstetrics and Gynecology, Shenzhen Hospital, Southern Medical University, No. 1333, Xinhu Road, Shenzhen, 518000, China.
Department of Reproductive Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, China.
Reprod Biol Endocrinol. 2021 Feb 23;19(1):29. doi: 10.1186/s12958-021-00718-z.
Long noncoding RNAs (lncRNAs) participate in the pathogenesis of various human diseases. This study aims to investigate the roles of lncRNA LINC00477 in polycystic ovary syndrome (PCOS), especially the impacts of LINC00477 on the proliferation and migration of human granulosa cells and the related mechanisms.
qRT-PCR analysis was performed to examine the expression pattern of LINC00477 in serum samples of PCOS patients as well as PCOS animal models. The effect of LINC00477 on the viability and apoptosis of ovarian granulosa cells was detected by MTT and flow cytometry assays. The correlation between LINC00477 and miR-128 was verified by bioinformatics analysis and dual-luciferase reporter and RNA pull-down assays. Finally, rescue assays were performed to analyze the effects of the LINC00477-miR-128 axis on the biological behaviors of granulosa cells.
LINC00477 was significantly upregulated in the serum of PCOS patients as well as PCOS mouse models. LINC00477 overexpression inhibited the proliferation and promoted the apoptosis of granulosa cells, whereas knockdown of LINC00477 yielded the opposite effects. Moreover, miR-128 mimics partially abrogated the effect of LINC00477 on granulosa cells.
LINC00477 may function as a ceRNA to inhibit proliferation and apoptosis of granulosa cells by modulating miR-128 expression.
长链非编码 RNA（lncRNA）参与了多种人类疾病的发病机制。本研究旨在探讨 lncRNA LINC00477 在多囊卵巢综合征（PCOS）中的作用，特别是 LINC00477 对人卵巢颗粒细胞增殖和迁移的影响及其相关机制。
通过 qRT-PCR 分析检测 PCOS 患者血清样本和 PCOS 动物模型中 LINC00477 的表达模式。通过 MTT 和流式细胞术检测 LINC00477 对卵巢颗粒细胞活力和凋亡的影响。通过生物信息学分析和双荧光素酶报告基因及 RNA 下拉实验验证 LINC00477 与 miR-128 之间的相关性。最后，通过 rescue 实验分析 LINC00477-miR-128 轴对颗粒细胞生物学行为的影响。
LINC00477 在 PCOS 患者血清和 PCOS 小鼠模型中均显著上调。LINC00477 过表达抑制颗粒细胞增殖并促进其凋亡，而敲低 LINC00477 则产生相反的效果。此外，miR-128 模拟物部分逆转了 LINC00477 对颗粒细胞的作用。
LINC00477 可能通过调节 miR-128 的表达，作为 ceRNA 抑制颗粒细胞的增殖和凋亡。
