Oncotarget

Research Papers:

miR-29a regulated ER-positive breast cancer cell growth and invasion and is involved in the insulin signaling pathway

Zhi-hua Li _, Qiu-yun Xiong, Liang Xu, Peng Duan, Qianwen Ou Yang, Ping Zhou and Jian-hong Tu

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Oncotarget. 2017; 8:32566-32575. https://doi.org/10.18632/oncotarget.15928

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Abstract

Zhi-hua Li1, Qiu-yun Xiong1, Liang Xu1, Peng Duan2, Qianwen Ou Yang1, Ping Zhou1, Jian-hong Tu3

1Prevention and Cure Center of Breast Disease, The Third Hospital of Nanchang City, Key Laboratory of Breast Diseases in Jiangxi Province, Nanchang, JiangXi 330009, People’s Republic of China

2Department of Endocrinology, The Third Hospital of Nanchang City, Nanchang Key Laboratory of Diabetes, Nanchang, JiangXi 330009, People’s Republic of China

3Pathology Department, The Third Hospital of Nanchang City, JiangXi Breast Specialist Hospital, Nanchang, JiangXi 330009, People’s Republic of China

Correspondence to:

Zhi-hua Li, email: huazhili0802@163.com

Qiu-yun Xiong, email: xqy6235100@163.com

Keywords: MiR-29a, breast cancer, insulin signaling pathway, cell proliferation, invasion

Received: October 24, 2016     Accepted: February 15, 2017     Published: March 06, 2017

ABSTRACT

Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration. We found that miR-29a-induced cell proliferation and metastasis acceleration occurred primarily through ERK phosphorylation. The IGF-1R is the upstream target gene of miR-29a, while CDC42 and p85α are the downstream target genes of miR-29a. These results have provided us with information regarding the molecular mechanisms by which hyperinsulinemia promotes breast cancer occurrence and development and thus leads to a poor prognosis in breast cancer patients and indicate that miR-29a plays an important role in breast cancer development and invasion.


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