CircSEPT9 promotes breast cancer progression by regulating PTBP3 expression via sponging miR-625-5p

Sep 21, 2026

Background: Breast cancer threatens women’s health, and circular RNAs are key regulators in multiple cancers. The study investigates how circular RNA Septin 9 (circSEPT9) drives breast cancer progression. Methods: circSEPT9, miR-625-5p, and PTBP3 were measured by qRT-PCR; PTBP3, E-cadherin, and vimentin by Western blot. Functional assays included CCK-8, EDU, apoptosis by flow cytometry, migration by Transwell and wound healing, and glycolytic readouts plus dual-luciferase and RIP. Results: circSEPT9 was upregulated; silencing reduced proliferation, migration, EMT, and glycolysis while enhancing apoptosis, and impaired tumor growth in vivo. miR-625-5p targeted circSEPT9 and reversed these effects by modulating PTBP3. Conclusion: circSEPT9 promotes malignant progression through the circSEPT9/miR-625-5p/PTBP3 axis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Background on breast cancer

Roles of circular RNAs and microRNAs

PTBP3 and research rationale

Methods

DOI: 10.1111/1759-7714.15252 ORIGINA L ARTICLE CircSEPT9 promotes breast cancer progression by regulating PTBP3 expression via sponging miR-625-5p Guangtao Shi 1 | Hongbo Li 2 | Ying Chen 2 | Zhi Chen 2 | Xiaoji Lin 2 1Zhejiang Society for Mathematical Medicine, Hangzhou, China 2Oncology Discipline Group, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, China Correspondence Xiaoji Lin, Oncology Discipline Group, The Second Affiliated Hospital of Wenzhou Medical University, No.1111 Wenzhou Avenue, Longwan District, Wenzhou City, 325000, Zhejiang, China. Email: [linxiaoji321@163.com](linxiaoji321@163.com) Abstract Background: Breast cancer (BC) is a common malignancy which threatens the health of women. Circular RNAs (circRNAs) are critical factors in multiple cancers, including BC. The aim of this experiment was to investigate the molecular mechanisms ofcircRNA Septin 9 (circSEPT9) in the progression of BC. Methods: CircSEPT9, microRNA-625-5p (miR-625-5p) and polypyrimidine tractbinding protein 3 (PTBP3) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) . Western blot was performed to detect the protein levels of PTBP3, E-cadherin and vimentin. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-20-deoxyuridine (EDU) was utilized for proliferation examination. Flow cytometry was conducted to measure apoptosis. Transwell assay and wound healing assay to investigate the migration of BC cells. Glucose uptake and lactate production were determined by specific kits. Additionally, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the interaction. A murine xenograft model was established to investigate the function of circSEPT9 in BC in vivo. Results: Overexpression of circSEPT9 was found in BC tissues and cells. Silencing circSEPT9 impeded BC cell proliferation, migration, epithelial–mesenchymal transition (EMT) and glycolytic metabolism but facilitated cell apoptosis in vitro. Meanwhile, circSEPT9 knockdown constrained tumor growth in vivo. MiR-625-5p was targeted by circSEPT9 . The influence of silencing circSEPT9 on BC cell function was regained by miR-625-5p inhibitor. Furthermore, miR-625-5p regulated BC cell malignant phenotypes via downregulating PTBP3 . Conclusion: circSEPT9 contributed to the malignant progression of BC by upregulating PTBP3 via sponging miR-625-5p. KEYW ORD S breast cancer, circSEPT9, miR-625-5p, PTBP3 INTRODUCTION All over the world, breast cancer (BC) is a prevalent malignancy influencing the physical and mental health of women.1 Global cancer data has revealed that there are 2 million new cases of BC in females each year.2 The prevalence of BC is rising in a rapid manner in China.3 Moreover, Guangtao Shi and Hongbo Li contributed equally to this study. advanced BC is usually difficult to treat and the prognosis of the disease is poor.4,5 Therefore, exploring the pathogenesis of BC and seeking diagnostic markers for BC are of great importance for female health. Increasing evidence suggests that noncoding RNAs (ncRNAs) are widely engaged in regulating cancer course.6 As a type of ncRNAs, circular RNAs (circRNAs) are formed from precursor RNA with a closed covalent loop structure.7,8 Owing to the stability, abundance and evolutionary This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd. conservation among species, circRNAs are engaged in extensive biological processes in tumors.9,10 For example, knockdown of circ_ 0068631 remarkably retarded the proliferation and migration of BC cells.11 CircCNOT2 silencing facilitated apoptosis and arres

FAQs

What is the main purpose of studying circSEPT9 in breast cancer?

To investigate the molecular mechanism by which circSEPT9 regulates breast cancer progression, focusing on its relationship with miR-625-5p and PTBP3.

How does circSEPT9 affect breast cancer cells and tumors?

Overexpression is found in breast cancer, while silencing circSEPT9 inhibits proliferation, migration, EMT, and glycolytic metabolism and promotes apoptosis; knockdown also constrains tumor growth in vivo.

What molecular interactions connect circSEPT9, miR-625-5p, and PTBP3?

circSEPT9 targets and sponges miR-625-5p, and miR-625-5p regulates breast cancer malignant phenotypes by downregulating PTBP3; inhibiting miR-625-5p can rescue the effects of circSEPT9 knockdown.

Sep 21, 2026

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