miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

// Wei Dang 1, 2, 3, * , Zailong Qin 1, 2, 3, * , Songqing Fan 4 , Qiuyuan Wen 4 , Yuanjun Lu 1, 2, 3 , Jia Wang 1, 2, 3 , Xuemei Zhang 1, 2, 3 , Lingyu Wei 1, 2, 3 , Wei He 2, 5 , Qiurong Ye 1, 2, 3 , Qun Yan 6 , Guiyuan Li 1, 2, 3 , Jian Ma 1, 2, 3 1 Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China 2 Cancer Research Institute, Central South University, Changsha, Hunan, China 3 Hunan 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 4 Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China 5 Xi’an Children’s Hospital, Xi’an, Shaanxi, China 6 Department of Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, Hunan, China * These authors contributed equally to this work Correspondence to: Jian Ma, email: majian@csu.edu.cn Keywords: miR-1207-5p, CSF1, macrophage, tumor microenvironment, lung cancer Received: November 01, 2015      Accepted: March 29, 2016      Published: April 13, 2016 ABSTRACT 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.