Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway

Cell Death Dis. 2018 Jan 24;9(2):91. doi: 10.1038/s41419-017-0128-y.

Mengwei Li ¹ ², Yanzhen Han ¹ ², Haoze Zhou ¹ ², Xin Li ¹ ², Chenyu Lin ¹ ², Erhao Zhang ¹ ², Xiaowei Chi ¹ ², Jialiang Hu ³ ⁴, Hanmei Xu ⁵ ⁶

Affiliations

1 The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, 210009, China.
2 State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
3 The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, 210009, China. Jialiang_hu51@aliyun.com.
4 State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China. Jialiang_hu51@aliyun.com.
5 The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, 210009, China. 13913925346@126.com.
6 State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China. 13913925346@126.com.

PMID: 29367600 DOI: 10.1038/s41419-017-0128-y

Abstract

The identification of specific drug targets guides the development of precise Cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast Cancer. We integrate the MicroRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases in clinical breast Cancer tissues, and find that miR-27a is significantly upregulated and correlated with poor survival outcome and tumor progression. Transmembrane protein 170B (TMEM170B), a new functional target of miR-27a, is identified via target prediction and experimental validation, suppressing breast Cancer proliferation, metastasis, and tumorigenesis. Furthermore, TMEM170B overexpression promotes cytoplasmic β-catenin phosphorylation, resulting in the inhibition of β-catenin stabilization, reduction of nuclear β-catenin levels and downstream targets expression. Clinically, TMEM170B or β-catenin expression is significantly correlated with overall survival ratio in breast Cancer patients. Thus, these results highlight TMEM170B as a novel tumor suppressor target in association with the β-catenin pathway, which may provide a new therapeutic approach for human breast Cancer therapy.

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