RBM8A, a new target of TEAD4, promotes breast cancer progression by regulating IGF1R and IRS-2

Sep 21, 2026

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Breast cancer is the most common malignant tumor in women worldwide, and improving patient prognosis requires deeper understanding of molecular mechanisms. RNA binding motif protein 8A (RBM8A) regulates diverse cancers, motivating investigation of its function in breast cancer. The study integrates bioinformatics, gene-expression assays, cell proliferation and apoptosis tests, RNA binding analyses, and in vivo xenograft validation to define RBM8A and TEAD4-driven regulatory pathways.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Keywords

Li et al. Journal of Translational Medicine (2024) 22:823 [https://doi.org/10.1186/s12967-024-05639-0](https://doi.org/10.1186/s12967-024-05639-0) Journal of Translational Medicine RESEARCH Open Access RBM8A, a new target ofTEAD4, promotes breast cancer progression by regulating IGF1Rand IRS-2 Fang Li2†, Xiaofei Wang3†, Jing Zhang4,5, Jinyuan Zhang2, Xintao Jing2, Qiuyu Jiang2, Jing Zhou2, Li Cao2, Hang Peng6, Dongdong Tong2* and Chen Huang 1,2,3* Abstract Background Breast cancer (BC) is the most common malignant tumor in women worldwide, and further elucidation of the molecular mechanisms involved in BC pathogenesis is essential to improve the prognosis of BC patients. RNA Binding Motif Protein 8 A (RBM8A), with high affinity to a myriad of RNA transcripts, has been shown to play a crucial role in genesis and progression of multiple cancers. We attempted to explore its functional significance and molecular mechanisms in BC. Methods Bioinformatics analysis was performed on publicly available BC datasets. qRT-PCR was used to determine the expression of RBM8A in BC tissues. MTT assay, clone formation assay and flow cytometry were employed to examine BC cell proliferation and apoptosis in vitro. RNA immunoprecipitation (RIP) and RIP-seq were used to investigate the binding of RBM8A/EIF4A3 to the mRNA of IGF1R/IRS-2 . RBM8A and EIF4A3 interactions were determined by co-immunoprecipitation (Co-IP) and immunofluorescence. Chromatin immunoprecipitation (Ch-IP) and dual-luciferase reporter assay were carried out to investigate the transcriptional regulation of RBM8A byTEAD4 . Xenograft model was used to explore the effects of RBM8A andTEAD4 on BC cell growth in vivo. Results In this study, we showed that RBM8A is abnormally highly expressed in BC and knockdown of RBM8A inhibits BC cell proliferation and induces apoptosis in vitro. EIF4A3, which phenocopy RBM8A in BC, forms a complex with RBM8A in BC. Moreover, EIF4A3 and RBM8A complex regulate the expression of IGF1R and IRS-2 to activate the PI3K/AKT signaling pathway, thereby promoting BC progression. In addition, we identified TEAD4 as a transcriptional activator of RBM8A by Ch-IP, dual luciferase reporter gene and a series of functional rescue assays. Furthermore, we demonstrated the in vivo pro-carcinogenic effects ofTEAD4 and RBM8A by xenograft tumor experiments in nude mice. †Fang Li and Xiaofei Wang contributed equally to this work. *Correspondence: Dongdong Tong [tongdd@xjtu.edu.cn](tongdd@xjtu.edu.cn)[ ](tongdd@xjtu.edu.cn)Chen Huang [hchen@xjtu.edu.cn](hchen@xjtu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[creativecommons.org/l](creativecommons.org/l)icenses/by-nc-nd/4.0/. Li et al. Journal of Translational Medicine (2024) 22:823 Page 2 of 16 Conclusion Collectively, these findings suggest that TEAD4 novel transcriptional target RBM8A interacts with EIF4A3 to increase IGF1R and IRS-2 expression and acti

FAQs

What is the main focus of the study on breast cancer?

The study investigates how RBM8A functions as a new target regulated by TEAD4 and how this influences breast cancer progression through IGF1R and IRS-2.

How did the researchers assess RBM8A in breast cancer?

They used bioinformatics on public datasets and measured RBM8A expression in breast cancer tissues using qRT-PCR. They then evaluated cell proliferation and apoptosis using MTT, clone formation assays, and flow cytometry.

What signaling pathway is linked to RBM8A and TEAD4 activity?

The EIF4A3 and RBM8A complex regulates IGF1R and IRS-2 expression to activate the PI3K/AKT signaling pathway, promoting breast cancer progression.

Sep 21, 2026

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