CircATP5C1 promotes triple-negative breast cancer progression by binding IGF2BP2 to modulate CSF-1 secretion

Sep 23, 2026

Uploaded by Aurelia

Triple-negative breast cancer (TNBC) is a common and deadly malignancy lacking effective targeted therapies, and the roles of most circular RNAs in TNBC progression remain unclear. This study identifies a novel circRNA, circATP5C1, and evaluates its expression in TNBC tissue microarrays and patient prognosis. Functional assays and RNA-seq reveal downstream regulation. RNA pull-down, mass spectrometry, RNA FISH, immunofluorescence, and RIP confirm the interaction between circATP5C1 and IGF2BP2. Mechanistically, circATP5C1 promotes TNBC progression by binding IGF2BP2 to increase CSF-1 secretion through a circATP5C1/IGF2BP2/CSF-1 pathway.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Study objectives and clinical relevance

Methods and functional validation

Mechanism: circATP5C1/IGF2BP2/CSF-1 pathway

Article history and keywords

CANCER BIOLOGY & THERAPY 2025, VOL. 26, NO. 1, 2479926 [https://doi.org/10.1080/15384047.2025.2479926](https://doi.org/10.1080/15384047.2025.2479926) RESEARCH PAPER CircATP5C1 promotes triple-negative breast cancer progression by binding IGF2BP2 to modulate CSF-1 secretion Hongbo Liua, Haoqi Wanga, Wei Gaoa, Yang Yuana, Tiantian Tanga, Meixiang Sangb, Fei Liub, and Cuizhi Geng a aDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China; bResearch Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China ABSTRACT Triple-negative breast cancer (TNBC) is a common malignant disease among females and severely threatens the health of women worldwide. Nowadays, circular RNAs (circRNAs) aroused our interest for their functions in human cancers, including TNBC. However, the mechanism of most circRNAs in the progression of TNBC remains unclear. We found a novel circRNA named circATP5C1, whose function in TNBC remains uncovered. Tissue microarray was used to analyze the association between the expression of circATP5C1 and the prognoses of TNBC patients. Gain-and loss-of-function experiments were performed to validate the biological functions of circATP5C1 in different TNBC cell lines. RNA-seq analyses were conducted to find out the target genes regulated by circATP5C1 . RNA pull-down assay and mass spectrometry were used to select the proteins associated with circATP5C1 . RNA FISHimmunofluorescence and RNA immunoprecipitation (RIP) were complemented to validate the interaction between circATP5C1 and its binding protein. CircATP5C1 was identified to have predictive function in prognosis of TNBC patients. CircATP5C1 advanced the progression of TNBC cells. Mechanistically, Colony stimulating factor 1 (CSF-1) is a vital downstream gene regulated by circATP5C1 . The alteration of CSF-1 expression level was validated due to the interaction between circATP5C1 and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) . Rescue experiments demonstrated that circATP5C1 accelerates the progression of TNBC partly via binding with IGF2BP2 to increase the secretion of CSF-1 . This study uncovers a novel mechanism of circATP5C1/IGF2BP2/CSF-1 pathway in regulating progression of TNBC. ARTICLE HISTORY Received 17 November 2024 Revised 7 March 2025 Accepted 11 March 2025 KEYWORDS Triple-negative breast cancer; circATP5C1; IGF2BP2; CSF-1; EMT Introduction It was reported that there were 2.3 million new cases of breast cancer (BC) in 2020, accounting for nearly 12% of all new cancer cases, with 685 000 deaths in the same year. 1 Due to improvements in therapy and screening techniques, the mortality rate of patients with BC has declined in recent years.2 However, BC is still the leading cause of cancer-related deaths for women worldwide.3 Accounting for generally 15% of all breast cancers, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor CONTACT Fei Liu [kyzxlf@hebmu.edu.cn](kyzxlf@hebmu.edu.cn) Research Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, No. 169 Tianshan Street, Yuhua District, Shijiazhuang, Hebei Province 050017, China; Cuizhi Geng [46300349@hebmu.edu.cn](46300349@hebmu.edu.cn) Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province 050017, China Supplemental data for this article can be accessed online at [https://doi.org/10.1080/15384047.2025.2479926](https://doi.org/10.1080/15384047.2025.2479926) © 2025 The Fourth Hospital of Hebei Medical University. Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([http://creativecommons.org/licenses/by-nc/4.0/](http://creat

FAQs

What role does circATP5C1 play in triple-negative breast cancer progression?

circATP5C1 advances TNBC cell progression and is associated with predictive prognostic value in TNBC patients.

How does circATP5C1 influence CSF-1 secretion?

circATP5C1 binds the RNA-binding protein IGF2BP2, which modulates CSF-1 expression and increases CSF-1 secretion.

What experimental approaches were used to establish the circATP5C1 mechanism?

The study uses tissue microarrays, gain- and loss-of-function assays, RNA-seq, RNA pull-down with mass spectrometry, RNA FISH/immunofluorescence, RIP, and rescue experiments.

Sep 23, 2026

Uploaded by Aurelia