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Molecular Cancer
Published in: Molecular Cancer 1/2024

Open Access 01-12-2024 | Research

ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner

Authors: Chuanpeng Zhang, Ziyi Yu, Susu Yang, Yitao Liu, Jiangni Song, Juan Mao, Minghui Li, Yi Zhao

Published in: Molecular Cancer | Issue 1/2024

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Abstract

Background

Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated.

Methods

In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting.

Results

The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway.

Conclusion

Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC.
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Metadata
Title
ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner
Authors
Chuanpeng Zhang
Ziyi Yu
Susu Yang
Yitao Liu
Jiangni Song
Juan Mao
Minghui Li
Yi Zhao
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-024-01944-w

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