BACKGROUND Hepatocellular carcinoma (HCC) is a common tumor malignancy threatening a significant number of people worldwide. Although microRNAs (miRNAs) have been shown to play essential role in tumorigenesis, little is known about their role in T cells functions during HCC progression. METHODS The abundances of miR-26b-5p were detected in HCC tissues or cells, T cells and H22 cells by quantitative real-time polymerase chain reaction (qRT-PCR). Regulation effect of miR-26b-5p on proviral integrations of moloney virus 2 (PIM2) was investigated by qRT-PCR, western blot (WB) and immunohistochemical analysis. The effect of miR-26b-5p and PIM-2 on cytokines secretion in CD4+ and CD8+ cells was evaluated by commercial enzyme linked immunosorbent assays (ELISA) kit. The interaction between miR-26b-5p and PIM-2 was probed by luciferase activity and RNA immunoprecipitation (RIP). H22 subcutaneous model was established to investigate the interaction of miR-26b-5p with HCC and immune competence. RESULTS The abundance of miR-26b-5p was decreased in HCC and associated with poor survival. Addition of miR-26b-5p contributed to secretion of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-2 in CD4+ and CD8+ cells. Interestingly, PIM-2 was negatively regulated by miR-26b-5p and PIM-2 knockdown reversed anti-miR-26b-5p-mediated immunosuppression. Moreover, inhibitory effect of miR-26b-5p on HCC tumorigenesis was dependent on immune competence. CONCLUSIONS miR-26b-5p enhanced T cells responses by targeting PIM-2 in HCC, uncovering a promising therapeutic opportunity of HCC through reactivating immune system.

中文翻译：

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MicroRNA-26b-5p通过靶向肝细胞癌中的PIM-2增强T细胞反应。

背景技术肝细胞癌（HCC）是一种常见的恶性肿瘤，威胁着全世界的许多人。尽管已显示microRNA（miRNA）在肿瘤发生中起重要作用，但对于它们在HCC进展过程中在T细胞功能中的作用知之甚少。方法采用定量实时聚合酶链反应（qRT-PCR）方法在肝癌组织或细胞，T细胞和H22细胞中检测miR-26b-5p的丰度。通过qRT-PCR，western blot（WB）和免疫组化分析研究了miR-26b-5p对克隆病毒2（PIM2）的原病毒整合的调控作用。通过商业酶联免疫吸附测定（ELISA）试剂盒评估了miR-26b-5p和PIM-2对CD4 +和CD8 +细胞中细胞因子分泌的影响。miR-26b-5p和PIM-2之间的相互作用通过荧光素酶活性和RNA免疫沉淀（RIP）进行探测。建立H22皮下模型以研究miR-26b-5p与HCC和免疫能力的相互作用。结果在肝癌中miR-26b-5p的丰度降低，并且与不良的生存率相关。miR-26b-5p的添加有助于CD4 +和CD8 +细胞分泌肿瘤坏死因子α（TNF-α），干扰素-γ（IFN-γ），白介素6（IL-6）和IL-2。有趣的是，PIM-2被miR-26b-5p负调节，而PIM-2敲低则逆转了抗miR-26b-5p介导的免疫抑制作用。此外，miR-26b-5p对HCC肿瘤发生的抑制作用取决于免疫能力。结论miR-26b-5p通过靶向HCC中的PIM-2增强了T细胞反应，