Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells - Research overview

Sep 21, 2026

Uploaded by Hazel

Triple negative breast cancer requires new therapeutic targets. This study evaluates REG3A, a calcium-dependent lectin protein, by combining bioinformatics with analyses of human breast tissues and patient samples. REG3A expression is assessed, then its function is tested through genetic knockdown, CRISPR knockout, and overexpression in primary TNBC cells. Tumorigenic consequences are validated using subcutaneous xenograft models.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Jin et al. Breast Cancer Research (2024) 26:92 Breast Cancer Research [https://doi.org/10.1186/s13058-024-01845-2](https://doi.org/10.1186/s13058-024-01845-2) RESEARCH Open Access Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells Xiaoxia Jin 1, Shuyun Yang 1, Xiaoyun Lu 1, Xudong Chen 1* and Wencheng Dai2* Abstract Background Identifying new targets in triple negative breast cancer (TNBC) remains critical. REG3A (regenerating islet-derived protein 3 A), a calcium-dependent lectin protein, was thoroughly investigated for its expression and functions in breast cancer. Methods Bioinformatics and local tissue analyses were employed to identify REG3A expression in breast cancer. Genetic techniques were employed to modify REG3A expression, and the resulting effects on the behaviors of breast cancer cells were examined. Subcutaneous xenograft models were established to investigate the involvement of REG3A in the in vivo growth of breast cancer cells. Results Analysis of theTCGA database uncovered increased REG3A levels in human breast cancer tissues. Additionally, REG3A mRNA and protein levels were elevated inTNBC tissues of locally treated patients, contrasting with low expression in adjacent normal tissues. In primary human TNBC cells REG3A shRNA notably hindered cell proliferation, migration, and invasion while triggering caspase-mediated apoptosis. Similarly, employing CRISPRsgRNA for REG3A knockout showed significant anti-TNBC cell activity. Conversely, REG3A overexpression bolstered cell proliferation and migration. REG3A proved crucial for activating the Akt-mTOR cascade, as evidenced by decreased Akt-S6K1 phosphorylation upon REG3A silencing or knockout, which was reversed by REG3A overexpression. Aconstitutively active mutant S473D Akt1 (caAkt1) restored Akt-mTOR activation and counteracted the proliferation inhibition and apoptosis induced by REG3A knockdown in breast cancer cells. Crucially, REG3A played a key role in maintaining mTOR complex integrity. Bioinformatics identified zinc finger protein 680 (ZNF680) as a potential REG3A transcription factor. Knocking down or knocking out ZNF680 reduced REG3A expression, while its overexpression increased it in primary breast cancer cells. Additionally, enhanced binding between ZNF680 protein and the REG3A promoter was observed in breast cancer tissues and cells. In vivo, REG3A shRNA significantly inhibited primary TNBC cell xenograft growth. In REG3A-silenced xenograft tissues, reduced REG3A levels, Akt-mTOR inhibition, and activated apoptosis were evident. *Correspondence: Xudong Chen [13813755767@163.com](13813755767@163.com)[ ](13813755767@163.com)Wencheng Dai[ntimhotepcn@163.com](ntimhotepcn@163.com) 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 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line

FAQs

What is the main focus of the study on REG3A in triple negative breast cancer cells?

The study investigates whether increased REG3A expression drives tumorigenic behaviors in triple negative breast cancer cells and clarifies the underlying signaling mechanisms.

How did the researchers evaluate REG3A expression and its functional role?

They used bioinformatics and tissue analyses to measure REG3A expression, then applied genetic methods to modify REG3A levels and assessed effects on proliferation, migration, invasion, and apoptosis. In vivo xenograft models were also used.

Which signaling pathway is linked to REG3A’s effects?

REG3A is reported to activate the Akt-mTOR cascade, supported by reduced Akt-S6K1 phosphorylation after REG3A silencing or knockout and restoration of signaling when REG3A is overexpressed.

Sep 21, 2026

Uploaded by Hazel

Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells - Research overview_Page 1

Open in WPS to view all 18 pages