We aim to investigate the role of miR-98-mediated macrophage polarization in hepatocellular carcinoma (HCC) progression and to explore the underlying mechanism. A total of 25 paired HCC and matched adjacent normal tissues (ANTs) were collected. We incubated human blood monocytes isolated from healthy male donors with culture medium collected from HepG2 cells for 7 days. The mRNA and protein expression was detected by qRT-PCR and Western blot, respectively. Levels of cytokines secreted in culture medium were measured using the specific ELISA kits. The miR-98 mimic/inhibitor was transfected to explore the role of miR-98 in HCC-conditioned tumor-associated macrophages (TAMs). HepG2 cells were then cultured with condition medium from HCC-conditioned TAMs pretreated with miR-98 mimic/inhibitor, and cell migration and invasion assays were performed. Luciferase reporter assay was performed to analyze the interaction between miR-98 and interleukin (IL)-10. Our results showed that miR-98 was downregulated and IL-10 was upregulated in HCC tissues and HCC-conditioned TAMs. Further studies identified that IL-10 was a direct target gene of miR-98 in HCC-conditioned TAMs. Moreover, miR-98 regulated the levels of inflammatory cytokines in HCC-conditioned TAMs. HCC-conditioned TAMs pretreated with miR-98 regulated migration and invasion of HepG2 cells in vitro, and the effects were significantly reversed by IL-10. In conclusion, miR-98 not only regulated expression of inflammatory cytokines in HCC-conditioned TAMs, but also modulated the capacity of HCC-conditioned TAMs to regulate HepG2 cell migration and invasion, at least in part, by targeting IL-10. As a result, miR-98 may suppress the progress of HCC.

我们旨在调查miR-98介导的巨噬细胞极化在肝细胞癌（HCC）进展中的作用，并探讨其潜在机制。总共收集了25对HCC和匹配的邻近正常组织（ANTs）。我们用从HepG2细胞收集的培养基孵育了从健康男性供体中分离出的人类血液单核细胞7天。通过qRT-PCR和蛋白质印迹分别检测mRNA和蛋白质表达。使用特异性ELISA试剂盒测量培养基中分泌的细胞因子水平。转染了miR-98模拟物/抑制剂以探索miR-98在HCC条件的肿瘤相关巨噬细胞（TAM）中的作用。然后将HepG2细胞与来自经过miR-98模拟物/抑制剂预处理的HCC条件TAM的条件培养基一起培养，并进行细胞迁移和侵袭试验。进行荧光素酶报告基因分析以分析miR-98和白介素（IL）-10之间的相互作用。我们的结果表明，在肝癌组织和HCC调节的TAM中，miR-98被下调，而IL-10被上调。进一步的研究确定，IL-10是HCC条件TAM中miR-98的直接靶基因。而且，miR-98调节了HCC条件TAM中炎性细胞因子的水平。经miR-98预处理的HCC条件TAM调节了HepG2细胞的迁移和侵袭 miR-98调节HCC调节的TAM中炎性细胞因子的水平。经miR-98预处理的HCC条件TAM调节了HepG2细胞的迁移和侵袭 miR-98调节HCC调节的TAM中炎性细胞因子的水平。经miR-98预处理的HCC条件TAM调节了HepG2细胞的迁移和侵袭在体外，这种作用被IL-10明显逆转。总之，miR-98不仅调节HCC条件TAM中炎性细胞因子的表达，而且至少部分地通过靶向IL-10来调节HCC条件TAM调节HepG2细胞迁移和侵袭的能力。结果，miR-98可能抑制HCC的进展。