Open AccessIncreased T‐helper 17 cell differentiation mediated by exosome‐mediated micro RNA ‐451 redistribution in gastric cancer infiltrated T cells
Author(s) -
Liu Feng,
Bu Zhouyan,
Zhao Feng,
Xiao Daping
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13429
Subject(s) - exosome , microvesicles , pi3k/akt/mtor pathway , cancer cell , flow cytometry , chemistry , cancer research , ampk , cell , microrna , microbiology and biotechnology , biology , cancer , signal transduction , kinase , protein kinase a , biochemistry , genetics , gene
Micro RNA (miR)‐451 is a cell metabolism‐related mi RNA that can mediate cell energy‐consuming models by several targets. As miR‐451 can promote mechanistic target of rapamycin ( mTOR ) activity, and increased mTOR activity is related to increased differentiation of T‐helper 17 (Th17) cells, we sought to investigate whether miR‐451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR . Real‐time PCR was used for detecting expression of miR‐451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry ( IHC ). Immunofluorescence staining was used in monitoring the exosome‐enveloped miR‐451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR‐451 decreased significantly in gastric cancer ( GC ) tissues but increased in infiltrated T cells and exosomes; tumor miR‐451 was negatively related to infiltrated T cells and exosome miR‐451. Exosome miR‐451 can not only serve as an indicator for poor prognosis of post‐operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR‐451 can redistribute 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 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR‐451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR‐451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity.