microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma

Journal of Hematology & Oncology

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

 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.

【 图 表 】

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