Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology(Shandong University), Ministry of Education, Shandong Provincial Clinical Medicine Research Center for reproductive health, Shandong Provincial Key Laboratory of Reproductive Medicine, No.157 Jingliu Road, Jinan 250001, China.
EBioMedicine. 2018 Oct;36:526-538. doi: 10.1016/j.ebiom.2018.09.043. Epub 2018 Oct 5.
Disordered folliculogenesis is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear.
Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs) derived from women with and without PCOS were analyzed using microarray and qRT-PCR. Immortalized human granulosa cell lines were cultured for proliferation assays after transfection with the LINC-01572:28 over-expression vector in the presence or absence of p27 siRNA. Protein expression analysis, rescue assays, and RNA immunoprecipitation (RIP) were used to confirm the LINC-01572:28 substrate.
LINC-01572:28 and p27 protein were elevated whereas proliferating cell nuclear antigen protein was decreased in the hLGCs of women with PCOS. LINC-01572:28 expression was positively correlated with basal testosterone levels. Over-expression of LINC-01572:28 inhibited cell proliferation and impeded G1/S transition, which were partially reversed by siRNA-mediated p27 knockdown.
Our findings, therefore, suggest that LINC-01572:28 suppresses cell proliferation and cell cycle progression by reducing the degradation of p27 protein via SKP2 binding.
卵泡发生障碍是多囊卵巢综合征（PCOS）的一个主要特征，但潜在的分子机制尚不清楚。
采用微阵列和 qRT-PCR 分析来自有无 PCOS 女性的黄体化颗粒细胞（hLGC）中的长非编码 RNA（lncRNA）表达。在存在或不存在 p27 siRNA 的情况下，用 LINC-01572：28 过表达载体转染永生化人颗粒细胞系，进行增殖测定。采用蛋白质表达分析、挽救实验和 RNA 免疫沉淀（RIP）来确认 LINC-01572：28 的底物。
在 PCOS 女性的 hLGC 中，LINC-01572：28 和 p27 蛋白升高，而增殖细胞核抗原蛋白降低。LINC-01572：28 的表达与基础睾酮水平呈正相关。LINC-01572：28 的过表达抑制细胞增殖并阻碍 G1/S 期过渡，这部分被 siRNA 介导的 p27 敲低所逆转。
因此，我们的研究结果表明，LINC-01572：28 通过与 SKP2 结合减少 p27 蛋白的降解来抑制细胞增殖和细胞周期进程。
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