IGF2BP1 promotes endometriosis by enhancing m6A modification stability of HMGB1

Abstract

Background

Endometriosis is a chronic inflammatory condition afflicting women of reproductive age. Our study aims to clarify the function and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and high mobility group box 1 protein (HMGB1) in endometriosis.

Methods

HMGB1 and various N6-methyladenosine (m6A) reader protein levels were assessed in normal, eutopic, and ectopic endometrial tissue, and a correlation analysis was conducted. The impact of IGF2BP1 knockdown on endometriosis was assessed both in vivo in rat models and in vitro in ectopic endometrial stromal cells (eESCs) using methods such as immunoblotting and mRNA quantification. The binding of IGF2BP1 to HMGB1 mRNA in eESCs was assessed using RIP-PCR. Following transfection with sh-IGF2BP1 and oe-HMGB1, the expression of IGF2BP1 and HMGB1, as well as cell proliferation, invasion, and migration abilities, were measured in eESCs.

Results

In ectopic endometrial tissue, IGF2BP1 and HMGB1 were elevated and positively correlated. Inhibition of IGF2BP1 reduced eESC proliferation, migration, invasion, and glucose intake. Meanwhile, HMGB1, PKM2, and HK2 expression were depressed. In vivo, results were consistent with in vitro. Additionally, in vivo experiments confirmed that inhibition of IGF2BP1 resulted in reduced ectopic endometrial lesion spherical volume, weight, and interstitial lesions. IGF2BP1 bound to HMGB1 mRNA and enhanced its stability by m6A modification. Conversely, when IGF2BP1 was knocked down and HMGB1 was overexpressed, the results were opposite to those observed previously.

Conclusion

IGF2BP1 promotes endometriosis progression by enhancing m6A modification stability of HMGB1. This study provides a theoretical basis for identifying therapeutic targets for endometriosis.