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Updated: Aug 13, 2025

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
circAR-E2E4-miR-665-STAT3 axis is a potential regulatory network in triple-negative breast cancer
Hao Xu1,2, Mengdie Fang1, Bowen Zuo1
1School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310013, China.
Abstract:
Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs (ncRNA). Many studies showed that circRNAs played different biological functions in triple-negative breast cancer (TNBC). However, the potential molecular mechanism of circRNAs in TNBC still remains to be investigated. In this study, circAR-E2E4 was defined as a novel circRNA involved in TNBC progression, derived from and regulated by androgen receptor (AR). CCK-8 assay showed circAR-E2E4 regulated TNBC cell proliferation. Potential binding miRNAs of circAR-E2E4 were predicted and miR-665 was identified to have a great prognosis value. Three databases were employed to predict target genes of miR-665, and STAT3 was regarded as the most potential downstream genes analyzed by protein-protein interaction (PPI), hub gene screening, correlation analysis, and survival analysis. Finally, knockdown of circAR-E2E4 led to the decrease of STAT3 expression. Collectively, the regulatory network circAR-E2E4-miR-665-STAT3 axis we constructed was associated with TNBC progression, providing a promising diagnostic, prognostic, and therapeutic target in future treatment for TNBC.
Insights
This study identifies circAR-E2E4 as a novel circular RNA (circRNA) that promotes triple-negative breast cancer (TNBC) progression by regulating the miR-665-STAT3 axis. This axis offers potential diagnostic and therapeutic targets for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are emerging as key regulators in various cancers.
- The specific roles and mechanisms of circRNAs in triple-negative breast cancer (TNBC) require further elucidation.
Purpose of the Study:
- To investigate the function and molecular mechanism of a novel circRNA, circAR-E2E4, in the progression of triple-negative breast cancer (TNBC).
- To identify the regulatory network involving circAR-E2E4, its downstream targets, and its impact on TNBC development.
Main Methods:
- Identification and characterization of circAR-E2E4 derived from and regulated by the androgen receptor (AR).
- CCK-8 assay to assess the effect of circAR-E2E4 on TNBC cell proliferation.
- Bioinformatic prediction and experimental validation of miRNA (miR-665) and target gene (STAT3) interactions.
- Analysis of protein-protein interaction (PPI), hub gene screening, correlation, and survival analyses.
Main Results:
- circAR-E2E4 was identified as a novel circRNA involved in TNBC progression.
- circAR-E2E4 significantly regulates TNBC cell proliferation.
- The circAR-E2E4-miR-665-STAT3 axis was constructed, with STAT3 identified as a key downstream target.
- Knockdown of circAR-E2E4 decreased STAT3 expression, confirming the regulatory pathway.
Conclusions:
- The circAR-E2E4-miR-665-STAT3 regulatory axis plays a crucial role in TNBC progression.
- This axis represents a promising diagnostic, prognostic, and therapeutic target for future TNBC treatments.
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