Oncotarget

Research Papers:

Downregulation of miR-221-3p and upregulation of its target gene PARP1 are prognostic biomarkers for triple negative breast cancer patients and associated with poor prognosis

Ling Deng, Qianqian Lei, Yu Wang, Zhu Wang, Guiqin Xie, Xiaorong Zhong, Yanping Wang, Nianyong Chen, Yan Qiu, Tianjie Pu, Hong Bu and Hong Zheng _

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Oncotarget. 2017; 8:108712-108725. https://doi.org/10.18632/oncotarget.21561

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Abstract

Ling Deng1,*, Qianqian Lei1,2,*, Yu Wang1, Zhu Wang1, Guiqin Xie1, Xiaorong Zhong1, Yanping Wang1, Nianyong Chen3, Yan Qiu4, Tianjie Pu4, Hong Bu4 and Hong Zheng1,3

1Laboratory of Molecular Diagnosis of Cancer, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China

2Department of Radiation Oncology, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China

3Cancer center, West China Hospital, Sichuan University, Chengdu, China

4Department of Pathology, West China Hospital, Sichuan University, Chengdu, China

*These authors share co-first authorship

Correspondence to:

Hong Zheng, email: hzheng@scu.edu.cn

Keywords: triple negative breast cancer, prognosis, microRNA, miR-221-3p, PARP1

Received: November 26, 2015     Accepted: September 13, 2017     Published: October 06, 2017

ABSTRACT

The purpose of this study was to identify microRNAs (miRNAs) closely associated with the prognosis of triple-negative breast cancer (TNBC) and their possible targets. This study recruited 125 early-stage TNBC patients, including 40 cases in the experimental group (20 cases with poor prognoses vs. 20 cases with good prognoses) and 85 cases in the validation group (27 cases with poor prognoses vs. 58 cases with good prognoses). In the experimental group, miRNA microarray showed 34 differentially expressed miRNAs in patients with different prognoses. We selected 5 miRNAs for validation. The differential expression of miR-221-3p was further verified in the experimental and validation groups using real-time polymerase chain reaction (PCR). High miR-221-3p expression was associated with better 5-year disease-free survival (DFS) (HR = 0.480; 95% CI, 0.263–0.879; p = 0.017) of TNBC patients. High expression of its target gene PARP1 predicted poorer 5-year DFS (HR = 2.236, 95% CI, 1.209-4.136, p = 0.010). MiR-221-3p down-regulated PARP1 by targeting its 3'-untranslated region.

In conclusion, low miR-221-3p expression may contribute to the poor outcome of TNBC patients through regulating PARP1. MiR-221-3p likely plays a role as a PARP1 inhibitor by directly regulating PARP1 expression, thereby affecting the prognoses of TNBC patients.


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