open access

Vol 62, No 1 (2024)
Original paper
Submitted: 2023-11-14
Accepted: 2024-03-19
Published online: 2024-04-02
Get Citation

Inhibition of IGF2BP1 attenuates the progression of endometriosis through PTBP1

Yanlin Su1, Wencai Tian1, Li Cheng1, Ling Yin1, Xiaoxia He2, Xin Wei1
·
Pubmed: 38563050
·
Folia Histochem Cytobiol 2024;62(1):25-36.
Affiliations
  1. Department of Obstetrics and Gynecology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
  2. Department of Ultrasound, Joint Logistics Support Force 921 Hospital, Changsha, China

open access

Vol 62, No 1 (2024)
ORIGINAL PAPERS
Submitted: 2023-11-14
Accepted: 2024-03-19
Published online: 2024-04-02

Abstract

Introduction. Endometriosis (EMs), manifested by pain and infertility, is a chronic inflammatory disease. The precise pathophysiology of this disease remains uncertain. Insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and polypyrimidine tract-binding protein 1 (PTBP1) have both been found to regulate proliferation, apoptosis, and invasion. This study aimed to investigate the effects of IGF2BP1/PTBP1 in treating EMs.

Materials and methods. qRT-PCR and western blotting were employed to quantify IGF2BP1 and PTBP1 expression in six patients with EMs (mean age 33.83 years). The correlation analysis, STRING database prediction, and RNA immunoprecipitation were utilized to identify the relationship between IGF2BP1 and PTBP1. Ectopic endometrial volume, weight, HE staining, and IGF2BP1 silencing were utilized to estimate the effects of IGF2BP1 in EMs model rats. qRT-PCR, CCK-8, 5-ethynyl-2’-deoxyuridine (EDU) labeling, Transwell assay, and flow cytometry were utilized to assess the effects of IGF2BP1/PTBP1 on the proliferation, migration, invasion, and apoptosis of ectopic endometrial stromal cells (eESCs). Furthermore, western blotting was employed to evaluate expressions of PCNA, VEGF, and E-cadherin in EMs rats and eESCs.

Results. The mRNA and protein levels of IGF2BP1 and PTBP1 in the ectopic and eutopic endometrium of EMs patients were significantly increased. RNA immunoprecipitation revealed a close interaction of IGF2BP1 with PTBP1. Additionally, the endometrial volume, weight, and histopathologic scores in rats were significantly reduced after IGF2BP1 silencing. IGF2BP1 silencing also decreased the expression of PCNA and VEGF, and increased E-cadherin expression in endometrial tissues of EMs rats. Moreover, IGF2BP1 silencing inhibited proliferation, migration, and invasion and promoted apoptosis through PTBP1 in eESCs.

Conclusions. IGF2BP1 exhibits potential beneficial properties in the management of EMs by interacting with PTBP1, thereby highlighting IGF2BP1 as a promising therapeutic target for EMs.

Abstract

Introduction. Endometriosis (EMs), manifested by pain and infertility, is a chronic inflammatory disease. The precise pathophysiology of this disease remains uncertain. Insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and polypyrimidine tract-binding protein 1 (PTBP1) have both been found to regulate proliferation, apoptosis, and invasion. This study aimed to investigate the effects of IGF2BP1/PTBP1 in treating EMs.

Materials and methods. qRT-PCR and western blotting were employed to quantify IGF2BP1 and PTBP1 expression in six patients with EMs (mean age 33.83 years). The correlation analysis, STRING database prediction, and RNA immunoprecipitation were utilized to identify the relationship between IGF2BP1 and PTBP1. Ectopic endometrial volume, weight, HE staining, and IGF2BP1 silencing were utilized to estimate the effects of IGF2BP1 in EMs model rats. qRT-PCR, CCK-8, 5-ethynyl-2’-deoxyuridine (EDU) labeling, Transwell assay, and flow cytometry were utilized to assess the effects of IGF2BP1/PTBP1 on the proliferation, migration, invasion, and apoptosis of ectopic endometrial stromal cells (eESCs). Furthermore, western blotting was employed to evaluate expressions of PCNA, VEGF, and E-cadherin in EMs rats and eESCs.

Results. The mRNA and protein levels of IGF2BP1 and PTBP1 in the ectopic and eutopic endometrium of EMs patients were significantly increased. RNA immunoprecipitation revealed a close interaction of IGF2BP1 with PTBP1. Additionally, the endometrial volume, weight, and histopathologic scores in rats were significantly reduced after IGF2BP1 silencing. IGF2BP1 silencing also decreased the expression of PCNA and VEGF, and increased E-cadherin expression in endometrial tissues of EMs rats. Moreover, IGF2BP1 silencing inhibited proliferation, migration, and invasion and promoted apoptosis through PTBP1 in eESCs.

Conclusions. IGF2BP1 exhibits potential beneficial properties in the management of EMs by interacting with PTBP1, thereby highlighting IGF2BP1 as a promising therapeutic target for EMs.

Get Citation

Keywords

endometriosis; IGF2BP1; PTBP1; interaction

About this article
Title

Inhibition of IGF2BP1 attenuates the progression of endometriosis through PTBP1

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 62, No 1 (2024)

Article type

Original paper

Pages

25-36

Published online

2024-04-02

Page views

282

Article views/downloads

164

DOI

10.5603/fhc.98213

Pubmed

38563050

Bibliographic record

Folia Histochem Cytobiol 2024;62(1):25-36.

Keywords

endometriosis
IGF2BP1
PTBP1
interaction

Authors

Yanlin Su
Wencai Tian
Li Cheng
Ling Yin
Xiaoxia He
Xin Wei

References (31)
  1. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020; 382(13): 1244–1256.
  2. Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022; 379: e070750.
  3. Schindler AE. Dienogest in long-term treatment of endometriosis. Int J Womens Health. 2011; 3: 175–184.
  4. Yuan P, Meng L, Wang N. SOX12 upregulation is associated with metastasis of hepatocellular carcinoma and increases CDK4 and IGF2BP1 expression. Eur Rev Med Pharmacol Sci. 2017; 21(17): 3821–3826.
  5. Zhou J, Bi C, Ching YQ, et al. Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia. J Hematol Oncol. 2017; 10(1): 138.
  6. Huang X, Zhang H, Guo X, et al. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer. J Hematol Oncol. 2018; 11(1): 88.
  7. Li Q, Yang Li, Zhang F, et al. m6A methyltransferase METTL3 inhibits endometriosis by regulating alternative splicing of MIR17HG. Reproduction. 2023; 165(2): 197–208.
  8. Dorien FO, Fassbender A, Van Bree R, et al. Technical verification and assessment of independent validation of biomarker models for endometriosis. Biomed Res Int. 2019; 2019: 3673060.
  9. Zhu W, Zhou BL, Rong LJ, et al. Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis. J Zhejiang Univ Sci B. 2020; 21(2): 122–136.
  10. Zhao H, Hu S, Qi J, et al. Increased expression of HOXA11-AS attenuates endometrial decidualization in recurrent implantation failure patients. Mol Ther. 2022; 30(4): 1706–1720.
  11. Lebovic DI, Kir M, Casey CL. Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril. 2004; 82 Suppl 3: 1008–1013.
  12. Feng Y, Tan B, Dong H, et al. FoxA2 represses ERβ-mediated pyroptosis in endometriosis by transcriptionally inhibiting IGF2BP1. Exp Cell Res. 2023; 426(1): 113539.
  13. Cheng J, Li C, Ying Y, et al. Metformin alleviates endometriosis and potentiates endometrial receptivity decreasing VEGF and MMP9 and increasing leukemia inhibitor factor and HOXA10. Front Pharmacol. 2022; 13: 750208.
  14. Sancakli Usta C, Turan G, Bulbul CB, et al. Differential expression of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrium in ovarian endometriomas and their correlations with clinicopathological variables. Reprod Biol Endocrinol. 2020; 18(1): 116.
  15. Liu L, Bai Ru, Li D, et al. Promotes endometrial stromal cell proliferation and invasion in endometriosis via the /TRIM59 axis. Int J Genomics. 2022; 2022: 9083822.
  16. Zhao LY, Song J, Liu Y, et al. Mapping the epigenetic modifications of DNA and RNA. Protein Cell. 2020; 11(11): 792–808.
  17. Hogg SJ, Beavis PA, Dawson MA, et al. Targeting the epigenetic regulation of antitumour immunity. Nat Rev Drug Discov. 2020; 19(11): 776–800.
  18. Chen Y, Hong T, Wang S, et al. Epigenetic modification of nucleic acids: from basic studies to medical applications. Chem Soc Rev. 2017; 46(10): 2844–2872.
  19. Jiang X, Liu B, Nie Z, et al. The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021; 6(1): 74.
  20. Jiang Li, Zhang M, Wu J, et al. Exploring diagnostic m6A regulators in endometriosis. Aging (Albany NY). 2020; 12(24): 25916–25938.
  21. Li X, Xiong W, Long X, et al. Inhibition of METTL3/m6A/miR126 promotes the migration and invasion of endometrial stromal cells in endometriosis†. Biol Reprod. 2021; 105(5): 1221–1233.
  22. Liu Y, Guo Q, Yang H, et al. Allosteric regulation of IGF2BP1 as a novel strategy for the activation of tumor immune microenvironment. ACS Cent Sci. 2022; 8(8): 1102–1115.
  23. Mao Y, Jiang F, Xu XJ, et al. Inhibition of IGF2BP1 attenuates renal injury and inflammation by alleviating m6A modifications and E2F1/MIF pathway. Int J Biol Sci. 2023; 19(2): 593–609.
  24. Huang H, Weng H, Sun W, et al. Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018; 20(3): 285–295.
  25. Zhang L, Wan Y, Zhang Z, et al. IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. Theranostics. 2021; 11(3): 1100–1114.
  26. Delsouc MB, Conforti RA, Vitale DL, et al. Antiproliferative and antiangiogenic effects of ammonium tetrathiomolybdate in a model of endometriosis. Life Sci. 2021; 287: 120099.
  27. Liu S, Xin X, Hua T, et al. Efficacy of anti-VEGF/VEGFR agents on animal models of endometriosis: a systematic review and meta-analysis. PLoS One. 2016; 11(11): e0166658.
  28. Wang Y, Wei Y, Chen L, et al. Research progress of siVEGF complex and their application in antiangiogenic therapy. Int J Pharm. 2023; 643: 123251.
  29. Ellis K, Wood R. The comparative invasiveness of endometriotic cell lines to breast and endometrial cancer cell lines. Biomolecules. 2023; 13(6).
  30. Feng Y, Dong H, Zheng L. Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis. Pharm Biol. 2023; 61(1): 666–673.
  31. Huang Q, Gu S, Fang J, et al. A pan-cancer analysis of the oncogenic role of polypyrimidine tract binding protein 1 (PTBP1) in human tumors. Medicine (Baltimore). 2022; 101(52): e32428.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl