title: microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma.
abstract: BACKGROUND
  microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.
  
  
  METHODS
  Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC.
  
  
  RESULTS
  Ectopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC.
  
  
  CONCLUSIONS
  miR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. runout@163.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. runout@163.com.
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Chai
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. huxiaodong@gmail.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. huxiaodong@gmail.com.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. aojysili@126.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. aojysili@126.com.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Ao
authors.affiliation: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. wangwenquan@fudanpci.org.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. wangwenquan@fudanpci.org.|Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China. wangwenquan@fudanpci.org.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. gdm_325@163.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. gdm_325@163.com.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Gao
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China. kongjian198@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. zning818@163.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. zning818@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. bby570@gmail.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. bby570@gmail.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. yebogen@126.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. yebogen@126.com.
authors.forename: Bo-Gen
authors.initials: BG
authors.lastname: Ye
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. deningma@hotmail.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. deningma@hotmail.com.
authors.forename: De-Ning
authors.initials: DN
authors.lastname: Ma
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. doctortsai@163.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. doctortsai@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. sun.huichuan@zs-hospital.sh.cn.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. sun.huichuan@zs-hospital.sh.cn.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases