miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1
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Wei Dang1,2,3,*, Zailong Qin1,2,3,*, Songqing Fan4, Qiuyuan Wen4, Yuanjun Lu1,2,3, Jia Wang1,2,3, Xuemei Zhang1,2,3, Lingyu Wei1,2,3, Wei He2,5, Qiurong Ye1,2,3, Qun Yan6, Guiyuan Li1,2,3, Jian Ma1,2,3
1Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
2Cancer Research Institute, Central South University, Changsha, Hunan, China
3Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, Hunan, China
4Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
5Xi’an Children’s Hospital, Xi’an, Shaanxi, China
6Department of Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, Hunan, China
*These authors contributed equally to this work
Jian Ma, email: [email protected]
Keywords: miR-1207-5p, CSF1, macrophage, tumor microenvironment, lung cancer
Received: November 01, 2015 Accepted: March 29, 2016 Published: April 13, 2016
We previously reported that miR-1207-5p can inhibit epithelial-mesenchymal transition (EMT) induced by growth factors such as EGF and TGF-β, but the exact mechanism is unclear. Here we identified that Colony stimulating factor 1 (CSF1) is a target gene of miR-1207-5p. CSF1 controls the production, differentiation and function of macrophage and promotes the release of proinflammatory chemokines. We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings. miR-1207-5p overexpression can increase HUVEC angiogenesis, and can modulate the M2 phenotype of macrophage. miR-1207-5p also significantly inhibited A549 cells metastasis in a nude mouse xenograft model. miR-1207-5p and CSF1 expression levels and their relationship with lung cancer survival and metastasis status were assayed by means of a lung cancer tissue microarray. Macrophage is an essential part of the tumor microenvironment, thus the miR-1207-5p-CSF1 axis maybe a new regulator of lung cancer development through modulating the tumor microenvironment.
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