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Updated: Jan 30, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
The Interaction of CircESR1 and HNRNPAB Regulates Cell Cycle Transition of Breast Cancer Cell
Junchao Xu1,2,3,4, Qiao Xu5, Tingfang Cao1,2,3
1Department of Oncology, The First Affiliated Hospital of USTC, State Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, China.
Abstract:
The mechanisms by which circRNAs regulate estrogen receptor (ER)-positive breast progression and therapeutic resistance remain poorly defined. By screening circRNAs involved in ER signaling, circESR1 was identified as a novel circRNA exhibiting high specificity of expression in ER+ breast cancer. CircESR1 interacted with HNRNPAB, which was transcriptionally activated by ER/SP1 signaling. HNRNPAB promoted the back-splicing and expression of circESR1 by binding to the Alu elements of cognate pre-mRNA; and circESR1 transcripts increased the stability and expression of HNRNPAB, ensuring an efficient positive feedback loop as reflected in antiestrogen-resistant breast cancer cells. Furthermore, HNRNPAB interacted and stabilized CDK1 and CDK6 mRNA, which was facilitated by its asymmetrical binding of circESR1, to promote cell cycle progression. Patients whose cancer exhibited high levels of circESR1 and/or HNRNPAB exhibited advanced prognostic stage and poor survival. Combined use of circESR1 ASO and CDK4/6 inhibitors were shown to be an effective therapeutic approach overcoming antiestrogen resistance in breast cancer xenograft models. Hence, these findings elucidated a novel signaling complex centered around circESR1 and HNRNPAB in ER+ breast cancer, and suggested that circESR1 might represent a potential therapeutic target for this disease.
Insights
Circular RNAs (circRNAs) like circESR1 play a key role in estrogen receptor-positive breast cancer progression and resistance to endocrine therapy. Targeting circESR1 and HNRNPAB offers a promising therapeutic strategy for overcoming treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Estrogen receptor (ER)-positive breast cancer progression and therapeutic resistance mechanisms involving circular RNAs (circRNAs) are not fully understood.
- circRNAs are emerging as critical regulators in various cancers, including breast cancer.
Purpose of the Study:
- To investigate the role of circRNAs in ER-positive breast cancer and identify novel therapeutic targets.
- To elucidate the molecular mechanisms by which circRNAs contribute to endocrine therapy resistance.
Main Methods:
- Screening of circRNAs involved in ER signaling pathway.
- Identification and characterization of circESR1 and its interaction with HNRNPAB.
- Analysis of the positive feedback loop between circESR1 and HNRNPAB.
- Investigation of HNRNPAB's role in cell cycle regulation via CDK1 and CDK6 mRNA stabilization.
- Correlation analysis of circESR1 and HNRNPAB expression with patient prognosis.
- Evaluation of circESR1 ASO combined with CDK4/6 inhibitors in breast cancer xenograft models.
Main Results:
- circESR1 was identified as a novel circRNA highly expressed in ER-positive breast cancer.
- A positive feedback loop between circESR1 and HNRNPAB was established, promoting antiestrogen resistance.
- HNRNPAB, stabilized by circESR1, promotes cell cycle progression by stabilizing CDK1 and CDK6 mRNA.
- High levels of circESR1 and/or HNRNPAB correlate with advanced stage and poor survival in breast cancer patients.
- Combined circESR1 ASO and CDK4/6 inhibitors effectively overcame antiestrogen resistance in preclinical models.
Conclusions:
- A novel signaling complex involving circESR1 and HNRNPAB is crucial for ER-positive breast cancer progression and therapeutic resistance.
- circESR1 represents a potential therapeutic target for overcoming endocrine resistance in breast cancer.
- The circESR1-HNRNPAB axis offers a promising therapeutic strategy for managing advanced ER-positive breast cancer.
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