miR-1271 inhibits ER&#x03B1; expression and confers letrozole resistance in breast cancer

Tao Yu; Hai-Ru Yu; Jia-Yi Sun; Zhao Zhao; Shuang Li; Xin-Feng Zhang; Zhi-Xuan Liao; Ming-Ke Cui; Juan Li; Chan Li; Qiang Zhang

doi:10.18632/oncotarget.22359

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Research Papers:

miR-1271 inhibits ERα expression and confers letrozole resistance in breast cancer

Tao Yu, Hai-Ru Yu, Jia-Yi Sun, Zhao Zhao, Shuang Li, Xin-Feng Zhang, Zhi-Xuan Liao, Ming-Ke Cui, Juan Li, Chan Li and Qiang Zhang _

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Oncotarget. 2017; 8:107134-107148. https://doi.org/10.18632/oncotarget.22359

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Abstract

Tao Yu1,2, Hai-Ru Yu2, Jia-Yi Sun2, Zhao Zhao1, Shuang Li1, Xin-Feng Zhang1, Zhi-Xuan Liao1, Ming-Ke Cui1, Juan Li1, Chan Li1 and Qiang Zhang1

1Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, P.R.China

2Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, P.R.China

Correspondence to:

Qiang Zhang, email: [email protected]

Keywords: estrogen receptor; miR-1271; letrozole; DDIT3; breast cancer

Received: March 31, 2017 Accepted: October 28, 2017 Published: November 09, 2017

ABSTRACT

Attenuation of estrogen receptor α (ERα) expression via unknown mechanism(s) is a hallmark of endocrine-resistant breast cancer (BCa) progression. Here, we report that miR-1271 was significantly down-regulated in letrozole-resistant BCa tissues and in letrozole-resistant BCa cells. miR-1271 directly targeted the chromatin of DNA damage-inducible transcript 3 (DDIT3) gene. miR-1271 expression level was inversely correlated to DDIT3 mRNA level in BCa biopsies. Form a mechanistic standpoint, reintroduction of exogenous miR-1271 could effectively restore ERα level via inhibiting DDIT3 expression, thereby potentiating letrozole sensitivity in BCa cells. Moreover, DDIT3 deregulation promoted letrozole-resistance by acting as a potent corepressor of ESR1 transcription. Taken together, we have identified that disruption of the miR-1271/DDIT3/ERα cascade plays a causative role in the pathogenesis of letrozole resistance in BCa.

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Research Papers:

miR-1271 inhibits ERα expression and confers letrozole resistance in breast cancer

Abstract