Journal of Hematology & Oncology | |
microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma | |
Hui-Chuan Sun1  Hao Cai1  De-Ning Ma1  Bo-Gen Ye1  Yuan-Yuan Zhang1  Ning Zhang1  Jian Kong3  Dong-Mei Gao1  Wen-Quan Wang2  Jian-Yang Ao1  Xiao-Dong Zhu1  Zong-Tao Chai1  | |
[1] Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, People’s Republic of China;Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China;Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China | |
关键词: Macrophages; M-CSF; Hepatocellular carcinoma; microRNA-26a; | |
Others : 1217409 DOI : 10.1186/s13045-015-0150-4 |
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received in 2015-02-20, accepted in 2015-05-06, 发布年份 2015 | |
【 摘 要 】
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.
【 授权许可】
2015 Chai et al.
【 预 览 】
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