Down-regulation of CXXC5 inhibits proliferation and extracellular matrix accumulation in uterine leiomyoma cells via the TGF-β/Smad pathway

L. He, L. Shen, Z. Wang, Y. Shen, Y. Gao, J. Qu, J. Sun

Article ID: 5027
Vol 36, Issue 2, 2022
DOI: https://doi.org/10.54517/jbrha5027
Received: 12 September 2021; Accepted: 12 September 2021; Available online: 9 May 2022; Issue release: 9 May 2022

Abstract

Uterine leiomyoma is a benign tumor of the smooth muscle in the uterus, with an incidence of 70%in all women. Numerous studies have shown that CXXC-type zinc finger protein 5 (CXXC5) is involvedin the development of various diseases. However, whether CXXC5 plays a role in the progression ofuterine leiomyoma is unknown. The expression of CXXC5 was evaluated by immunofluorescence (IF),immunohistochemistry (IHC) and western blot analysis, and CXXC5 was shown to be overexpressed inuterine leiomyoma tissues. The elevated expression levels of transforming growth factor-beta (TGF-β)/Smadpathway-related proteins (TGF-β1, p-Smad2 and p-Smad2) and extracellular matrix (ECM) key markers(MMP-2, MMP-9, ADAM10 and ADAM15) were measured through western blot analysis. The proliferationof uterine leiomyoma cells was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays, IHC staining detected the expression of proliferation marker Ki-67. Results showed thatTGF-β1 promoted the proliferation of uterine leiomyoma cells while silencing RNA and TGF-β1 inhibitorSB431542 suppressed this effect. The expression of ECM accumulation-related proteins collagen IV andfibronectin was examined via western blot analysis and IF staining. CXXC5 attenuation by silencing RNAand TGF-β1 inhibitor SB431542 suppressed TGF-β1-induced ECM accumulation in primary uterineleiomyoma cells. Silencing of CXXC5 and treatment with SB431542 restrained the TGF-β/Smad pathwayin TGF-β1-treated primary uterine leiomyoma cells. CXXC5 inhibition suppressed uterine leiomyoma cellproliferation and ECM accumulation by modulating the TGF-β/Smad pathway.


Keywords

CXXC5;TGF-β/Smad pathway;uterine leiomyoma


References

Supporting Agencies



Copyright (c) 2022 L. He, L. Shen, Z. Wang, Y. Shen, Y. Gao, J. Qu, J. Sun




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).