2. Academic Validation
  3. Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway

Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway

  • FASEB J. 2024 May 15;38(9):e23622. doi: 10.1096/fj.202302195R.
Xiaohong Que 1 2 3,  Lulu Ren 1 2 4,  Lin Yang 2,  Lemeng Wang 2 5,  Junzui Li 2 5,  Rongfeng Wu 1 2 4 5,  Qionghua Chen 1 2 3 5
Affiliations

Affiliations

  • 1 The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.
  • 2 Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
  • 3 The Graduate School of Fujian Medical University, Fuzhou, Fujian, China.
  • 4 Reproductive Medical Center, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
  • 5 School of Medicine, Xiamen University, Xiamen, Fujian, China.
PMID: 38703029 DOI: 10.1096/fj.202302195R
Abstract

Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative Real-Time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.

Keywords

BMPR1B‐AS1; IGF2BP2; SMAD1/5/9; decidualization; endometriosis.

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