MiR-145 modulation of TGF-β pathway attenuates EMT inhibition of Wilms’Tumor cell proliferation, invasion and migration

Abstract To explore the impact of miR-145 on the proliferation, migration, and invasion of Wilms' tumor G401 cells by attenuating EMT through modulation of the TGF-β pathway.A Wilms' tumor G401 cell line overexpressing miR-145 and a blank control group were established.The proliferation of Wilms' tumor cells was assessed using the CCK8 assay and colony formation experiments.The influence of miR-145 overexpression on the migration and invasion capabilities of these cells was evaluated through Transwell assays.Western blotting was used to analyze the expression of TGF-β pathway-related proteins,EMT-related proteins,and apoptosis-related proteins.Additionally,changes in apoptotic proteins post-treatment with cisplatin were examined via Western blot.An orthotopic Wilms' tumor mouse model was developed to assess the effect of miR-145 overexpression on tumor growth and cisplatin treatment response.CCK8,clonogenic formation,and Transwell assays indicated that miR-145 overexpression group exhibited reduced proliferation,migration,and invasion of Wilms' tumor cells compared to the control.Western blot results demonstrated that miR-145 overexpression suppressed EMT in Wilms' tumor by inhibiting the Smad-mediated TGF-β pathway.MiR-145 significantly induced apoptosis in these cells and improved the therapeutic response to cisplatin,diminishing drug resistance.The orthotopic Wilms' tumor mouse model validated that miR-145 inhibited primary tumor growth in the Wilms' tumor xenograft and enhanced cisplatin treatment response.Taken together,miR-145 inhibits EMT in Wilms' tumor by suppressing the Smad-mediated TGF-β pathway,effectively reducing cell proliferation,migration,and invasion.The miR-145/Smad/TGF-β/EMT axis emerges as a potential therapeutic target for Wilms' tumor..

Medienart:

Preprint

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

ResearchSquare.com - (2024) vom: 20. März Zur Gesamtaufnahme - year:2024

Sprache:

Englisch

Beteiligte Personen:

Zhou, Jun [VerfasserIn]
Wu, Zhiwei [VerfasserIn]
Zhu, Jian [VerfasserIn]
Song, Jialun [VerfasserIn]
Wang, Peng [VerfasserIn]
Zhao, Xinxin [VerfasserIn]
Liu, Ziping [VerfasserIn]
Lu, Songxian [VerfasserIn]
Shi, Hongguang [VerfasserIn]
Feng, Xiaojuan [VerfasserIn]
Zheng, Mingjun [VerfasserIn]
Du, Junpeng [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.21203/rs.3.rs-3991565/v1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XRA042992583