MicroRNA-26b-5p enhances T cell responses by targeting PIM-2 in hepatocellular carcinoma |
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| Institution: | 1. Department Three of Oncology, The First People''s Hospital of Shangqiu, 476100, Henan, China;2. Department of Gastroenterology, Henan Tumor Hospital, 450008, Henan, China;1. Biochemistry Department, Faculty of Pharmacy, Cairo University, Egypt;2. Pharmacy Department, National Liver Institute, Menoufia University, Egypt;3. Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Egypt;4. Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Egypt;1. Department of Nephrology, Universitätsmedizin Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany;2. Deutsches Rheumaforschungszentrum, Charitéplatz 1, 10117 Berlin, Germany;3. Department of Pathology, Universitätsmedizin Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany;1. Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Republic of Korea;2. Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung 25457, Republic of Korea;3. Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, Republic of Korea;4. School of Life Sciences, College of Natural Sciences, Kyungpook National University, Taegu 41566, Republic of Korea |
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| Abstract: | BackgroundHepatocellular 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.MethodsThe 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.ResultsThe 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.ConclusionsmiR-26b-5p enhanced T cells responses by targeting PIM-2 in HCC, uncovering a promising therapeutic opportunity of HCC through reactivating immune system. |
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