Dataset Information

MiR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.

ABSTRACT: Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice, suggesting that miR-7 could exert its tumor-suppressive function in PC. Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which significantly enhanced PC cell proliferation and inhibited cell apoptosis partly through activation of the MEK/ERK pathway and NF-?B pathway. Moreover, rescue experiments also showed that miR-7 suppressed PC cell proliferation and induced PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the MEK/ERK and NF-?B pathways. Taken together, these results suggest that miR-7/MAP3K9 is critically involved in PC progression and that miR-7 may be a potential target for PC treatment.

SUBMITTER: Xia J

PROVIDER: S-EPMC6171162 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.

Xia Jun J Cao Tong T Ma Cong C Shi Ying Y Sun Yu Y Wang Z Peter ZP Ma Jia J

Molecular therapy. Nucleic acids 20180822

Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell grow ...[more]

PMID: 30290304

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Project description:BackgroundExperimental autoimmune encephalomyelitis (EAE) is a model for inflammatory demyelinating diseases of the central nervous system (CNS), a group of autoimmune diseases characterized by inflammatory infiltration, demyelination, and axonal damage. miR-20a is dysregulated in patients with CNS inflammatory demyelinating diseases; however, the function of miR-20a remains unclear. In this study, we intended to explore the role of miR-20a in EAE.MethodsThe expression of miR-20a was detected by quantitative real-time PCR (qRT-PCR) in EAE mice and patients with MOG antibody-associated demyelinating diseases. CD4+ T cells of EAE mice were sorted, stimulated, and polarized with miR-20a knockdown. Activation and differentiation of CD4+ T cells were analyzed by flow cytometry. The expression of target gene Map3k9 was detected by qRT-PCR and western blot experiments. The binding of miR-20a to the 3' UTR of Map3k9 was tested by luciferase assays. The feasibility of miR-20a as a therapeutic target to alleviate the severity of EAE was explored by intravenous administration of miR-20a antagomirs to EAE mice.ResultsmiR-20a was upregulated in splenocytes and lymph node cells, CD4+ T cells, and spinal cords of EAE mice. Moreover, miR-20a knockdown did not influence the activation of antigen-specific CD4+ T cells but promoted their differentiation into Treg cells. Map3k9 was predicted to be a target gene of miR-20a. The expressions of Map3k9 and miR-20a were negatively correlated, and miR-20a knockdown increased the expression of Map3k9. In addition, miR-20a binded to the 3' UTR of Map3k9, and simultaneous knockdown of miR-20a and Map3k9 counteracted the enhanced differentiation of Tregs observed when miR-20a was knocked down alone. Furthermore, injection of miR-20a antagomirs to EAE mice reduced the severity of the disease and increased the proportion of Treg cells in peripheral immune organs.ConclusionsmiR-20a suppresses the differentiation of antigen-specific CD4+ T cells into Tregs in EAE by decreasing the expression of Map3k9. miR-20a antagomirs alleviate EAE, suggesting a new therapy for EAE and CNS inflammatory demyelinating diseases.

Dataset Information

MiR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.

Publications

miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.

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