MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial–mesenchymal transition of hepatocellular carcinoma

• Main Authors: Lei Li, Pengfei Sun, Chengsheng Zhang, Zongchao Li, Kai Cui, Wuyuan Zhou
• Format: Article
• Language: English
• Published: BMC 2018-07-01
• Series: Cancer Cell International
• Subjects: miR-98; Macrophage polarization; Tumor-associated macrophages; Epithelial–mesenchymal transition; Hepatocellular carcinoma
• Online Access: http://link.springer.com/article/10.1186/s12935-018-0590-3

Abstract Background Tumor-associated macrophages (TAMs) are generally recognized as a promoter of tumor progression. miR-98 has been shown to suppress the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. Here, we aim to investigate the role of miR-98-mediated macrophage polarization in HCC progression. Methods Human blood monocytes were isolated from healthy male donors and incubated with culture medium collected from HepG2 cells for 7 days. The phenotype of the macrophages was detected. The protein expression was detected by Western blot. Levels of cytokines secreted in culture medium were measured using the specific enzyme-linked immunosorbent assay kits. To explore the role of miR-98 in HCC-conditioned TAMs, HCC cells HepG2 and SMMC7721 were cultured with conditioned medium from HCC-conditioned TAMs that had been transfected with miR-98 mimic/inhibitor. Cell proliferation, migration and invasion assays were performed. Results HCC-conditioned TAMs possessed M2-like phenotype, including increased protein expression of CD163 and TNF-αlow, IL-1βlow, TGF-βhigh and IL-10high phenotype. HCC-conditioned TAMs also promoted proliferation, migration, invasion and EMT of HepG2 and SMMC7721 cells. Furthermore, miR-98 modulated macrophage polarization from M2 to M1 in HCC-conditioned TAMs, as evidenced by the alteration of M1- or M2-related cytokines. Moreover, miR-98 mimic significantly suppressed the HCC-conditioned TAMs-mediated promotion of cell migration, invasion and EMT in HepG2 and SMMC7721 cells compared with negative control, whereas miR-98 inhibitor exerted reversed effects. Conclusions miR-98 may play a vital role in regulating macrophage polarization, thereby suppressing the TAMs-mediated promotion of invasion and EMT in HCC.