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

// Zhi-hua Li 1 , Qiu-yun Xiong 1 , Liang Xu 1 , Peng Duan 2 , Qianwen Ou Yang 1 , Ping Zhou 1 , Jian-hong Tu 3 1 Prevention 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 2 Department of Endocrinology, The Third Hospital of Nanchang City, Nanchang Key Laboratory of Diabetes, Nanchang, JiangXi 330009, People’s Republic of China 3 Pathology 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.