近日，北京大学Qing Xue及其课题组发现，ERβ激活的LINC01018通过调控CDC25C/CDK1/CyclinB1通路促进子宫内膜异位症的发展。相关论文于2024年1月14日在线发表于国际学术期刊《遗传学报》。

研究人员表示，子宫内膜异位症是一种雌激素依赖性疾病。雌激素受体2（ESR2）基因编码的主要雌激素受体亚型雌激素受体β（ERβ），可介导雌激素在子宫内膜异位症中的作用。虽然选择性雌激素受体调节剂可以靶向ERβ，但由于ERβ的广泛分布，它们并不具有特异性。最近，长非编码RNA被认为与子宫内膜异位症有关。

因此，研究人员旨在探索和验证ERβ的下游调控机制，并研究长基因间非编码RNA1018（LINC01018）作为子宫内膜异位症非激素治疗的潜在作用。研究表明，异位子宫内膜组织中ESR2和LINC01018的表达水平升高，并发现ESR2和LINC01018的表达呈显著正相关。从机制上看，ERβ直接与位于LINC01018启动子区的雌激素反应元件结合，并激活LINC01018的转录。

在功能上，ERβ可通过LINC01018调节CDC25C/CDK1/CyclinB1通路，并在体外促进异位子宫内膜基质细胞增殖。与这些发现一致的是，在体内敲除LINC01018可抑制子宫内膜异位病灶的增殖。总之，这项研究表明，ERβ/LINC01018/CDC25C/CDK1/CyclinB1信号轴调控子宫内膜异位症的进展。

附：英文原文

Title: ERβ-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway

Author: anonymous

Issue&Volume: 2024/01/14

Abstract: Endometriosis refers to as an estrogen-dependent disease. Estrogen receptor β (ERβ), the main estrogen receptor subtype which is encoded by the estrogen receptor 2 (ESR2) gene, can mediate the action of estrogen in endometriosis. Although selective estrogen receptor modulators can target ERβ, they are not specific due to the wide distribution of ERβ. Recently, long noncoding RNAs have been implicated in endometriosis. Therefore, we aim to explore and validate the downstream regulatory mechanism of ERβ, and to investigate the potential role of long intergenic noncoding RNA 1018 (LINC01018) as a nonhormonal treatment for endometriosis. Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between ESR2 and LINC01018 expression. Mechanistically, ERβ directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription. Functionally, ERβ can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro. Consistent with these findings, the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo. In summary, our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

DOI: 10.1016/j.jgg.2023.12.012

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724000043