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- Title
miR-190 enhances endocrine therapy sensitivity by regulating SOX9 expression in breast cancer.
- Authors
Yu, Yue; Yin, Wen; Yu, Zhi-Hao; Zhou, Yan-Jun; Chi, Jiang-Rui; Ge, Jie; Cao, Xu-Chen
- Abstract
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.
- Subjects
HORMONE therapy; BREAST cancer; METASTATIC breast cancer; CATENINS; PROGESTERONE receptors; BREAST cancer treatment
- Publication
Journal of Experimental & Clinical Cancer Research (17569966), 2019, Vol 38, Issue 1, pN.PAG
- ISSN
1756-9966
- Publication type
Article
- DOI
10.1186/s13046-019-1039-9