ERβ-activated <i>LINC01018</i> promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway

Ruihui Lu; Jingwen Zhu; Xin Li; Cheng Zeng; Yan Huang; Chao Peng; Yingfang Zhou; Qing Xue

doi:10.1016/j.jgg.2023.12.012

Volume 51 Issue 6

Jun. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(6): 617-629

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

doi: 10.1016/j.jgg.2023.12.012

Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China

Funds:

We thank the National Natural Science Foundation of China (82271676) for funding support.

Received Date: 2023-09-19
Accepted Date: 2023-12-29
Rev Recd Date: 2023-12-23

Available Online: 2025-06-06

Publish Date: 2024-01-14

Abstract

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 the 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 the 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.
- Estrogen receptor β,
- Long intergenic noncoding RNA 1018 (LINC01018),
- Endometriosis,
- Cell cycle,
- Proliferation

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