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Updated: Jan 30, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
miR-190 enhances endocrine therapy sensitivity by regulating SOX9 expression in breast cancer
Yue Yu1,2,3,4, Wen Yin1,2,3,4, Zhi-Hao Yu1,2,3,4
1The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huan-Hu-Xi Road, Hexi District, Tianjin, 300060, China.
Background:
Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. Therapies targeting ERα have been successfully used in patients with ERα+ breast cancer. However, intrinsic or acquired resistance to anti-estrogen therapy presents a major challenge. The Wnt/β-catenin signaling pathway regulates various processes that are important for cancer progression, and emerging evidences have shown a close interaction between Wnt/β-catenin and ERα signaling. miR-190 is also involved in ER signaling and our previous study indicated that miR-190 suppresses breast cancer metastasis.
Methods:
The effect of miR-190 on breast cancer anti-estrogen sensitivity was investigated both in vitro and in vivo. The protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of the zinc-finger E-box binding homeobox 1/ ERα-miR-190-SRY-related high mobility group box 9 (ZEB1/ERα-miR-190-SOX9) axis.
Results:
miR-190 increased the anti-estrogen sensitivity of breast cancer cells both in vitro and in vivo. miR-190 inhibited Wnt/β-catenin signaling by targeting SOX9, and its expression inversely correlated with that of SOX9 in breast cancer samples. Furthermore, ERα and ZEB1 competitively regulated miR-190 expression.
Conclusions:
Our data uncover the ZEB1/ERα-miR-190-SOX9 axis and suggest a mechanism by which the Wnt/β-catenin signaling pathway is involved in breast cancer anti-estrogen therapy.
Insights
MicroRNA-190 enhances breast cancer sensitivity to anti-estrogen therapies by targeting SOX9 and inhibiting Wnt/β-catenin signaling. This study reveals the ZEB1/ERα-miR-190-SOX9 axis, offering new insights into overcoming treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a prevalent malignancy, with 70% of cases being hormone receptor-positive (ERα+).
- Anti-estrogen therapies are effective but face challenges due to intrinsic or acquired resistance.
- The Wnt/β-catenin pathway and microRNAs, like miR-190, are implicated in ERα signaling and cancer progression.
Purpose of the Study:
- To investigate the role of miR-190 in modulating breast cancer sensitivity to anti-estrogen therapy.
- To elucidate the molecular mechanisms underlying the interaction between miR-190, Wnt/β-catenin signaling, and ERα signaling.
Main Methods:
- In vitro and in vivo studies assessed miR-190's effect on breast cancer cell sensitivity.
- Western blotting and immunofluorescence analyzed protein expression and localization.
- Chromatin immunoprecipitation and dual-luciferase reporter assays validated the ZEB1/ERα-miR-190-SOX9 axis.
Main Results:
- miR-190 significantly increased breast cancer cell sensitivity to anti-estrogen treatment.
- miR-190 suppressed Wnt/β-catenin signaling by targeting SOX9, with inverse correlation observed in patient samples.
- Estrogen receptor alpha (ERα) and ZEB1 were found to competitively regulate miR-190 expression.
Conclusions:
- The study identifies the ZEB1/ERα-miR-190-SOX9 axis as a key regulatory mechanism.
- This axis provides a novel understanding of Wnt/β-catenin pathway involvement in breast cancer anti-estrogen therapy resistance.
- Findings suggest potential therapeutic strategies targeting this axis to improve treatment outcomes.
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