Oncotarget

Research Papers:

Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer

Mingjie Lu, Tongshan Wang, Mingfeng He, Wenfang Cheng, Ting Yan, Zebo Huang, Lan Zhang, Huo Zhang, Wei Zhu _, Yichao Zhu and Ping Liu

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Oncotarget. 2017; 8:23008-23019. https://doi.org/10.18632/oncotarget.14968

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Abstract

Mingjie Lu1,*, Tongshan Wang1,*, Mingfeng He2,*, Wenfang Cheng3, Ting Yan4, Zebo Huang1, Lan Zhang1, Huo Zhang1, Wei Zhu1, Yichao Zhu5,6, Ping Liu1

1Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China

2Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China

3Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China

4Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, PR China

5Department of Physiology, Nanjing Medical University, Nanjing 211166, PR China

6State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, PR China

*These authors have contributed equally to this work

Correspondence to:

Wei Zhu, email: zhuwei@njmu.edu.cn

Yichao Zhu, email: zhuyichao@njmu.edu.cn

Ping Liu, email: liu-ping@csco.org.cn

Keywords: miR-3622b-5p, ERBB2, cancer, proliferation, apoptosis

Received: July 18, 2016    Accepted: January 10, 2017    Published: February 01, 2017

ABSTRACT

Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3’-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells. MiR-3622b-5p was significantly down-regulated in breast and gastric cancer tissues. This down-regulation in ERBB2-positive breast and gastric cancer tissues was more obvious than that in ERBB2-negative breast and gastric cancer tissues. MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil. Taken together, miR-3622b-5p is involved in the proliferation and apoptosis of human ERBB2-positive cancer cells via targeting ERBB2/mTORC1 signaling pathway.


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