Increased Th17 cell differentiation mediated by Exosome-mediated miR-451 re-distribution in gastric cancer infiltrated T cells

Abstract

miR-451 is a cell metabolism related miRNA which can mediate cell energy consuming models by several targets. Since miR-451 can promote mTOR activity, and the increased mTOR activity was related to increased differentiation of Th17 cells, we sought to investigate whether miR-451 can re-distributed from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting the expression of miR-451 in gastric cancer, tumor infiltrated T cell and exosome, the distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry. Immunofluorescence staining was used in monitoring the exosome enveloped miR-451 from cancer cells to T cells with different treatment, and signaling pathway change was analyzed by western-blot. miR-451 was decreased significantly in gastric cancer tissues but increased in infiltrated T cells and exosome; tumor miR-451 was negatively related to infiltrated T cell and exosome miR-451. Exosome miR-451 can not only serve as an indicator for bad prognosis of the post-operation GC patients but also related to increased Th17 distribution in gastric cancer. miR-451 can re-distributed from cancer cells to T cells with low glucose treatment. Decreased 5′ AMP-activated protein kinase (AMPK) and increased mTOR activity was investigated in miR-451 re-distributed T cells and thus increase their th17 polarized differentiation. Exosome miR-451 derived from the tumor tissues and can serve as an indicator for bad prognosis. And re-distribution of miR-451 from cancer cells to infiltrated T cell in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity.

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