MiR-190 enhances endocrine therapy sensitivity by regulating SOX9 expression in breast cancer.

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-? (ER?) or/and progesterone receptor. Therapies targeting ER? have been successfully used in patients with ER?⁺ breast cancer. However, intrinsic or acquired resistance to anti-estrogen therapy presents a major challenge. The Wnt/?-catenin signaling pathway regulates various processes that are important for cancer progression, and emerging evidences have shown a close interaction between Wnt/?-catenin and ER? 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/ ER?-miR-190-SRY-related high mobility group box 9 (ZEB1/ER?-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/?-catenin signaling by targeting SOX9, and its expression inversely correlated with that of SOX9 in breast cancer samples. Furthermore, ER? and ZEB1 competitively regulated miR-190 expression.

Conclusions

Our data uncover the ZEB1/ER?-miR-190-SOX9 axis and suggest a mechanism by which the Wnt/?-catenin signaling pathway is involved in breast cancer anti-estrogen therapy.

SUBMITTER: Yu Y 

PROVIDER: S-EPMC6339391 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature