Journal
ONCOTARGETS AND THERAPY
Volume 13, Issue -, Pages 10693-10705Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S256669
Keywords
MALAT1; dendritic cells; AKT; mTOR; autophagy
Categories
Funding
- National Natural Sciences Foundation of China [81772499, 81572287, 81974088]
- Health Commission of Hubei Province Scientific Research Project [WJ2017M142]
- Natural Science Foundation of Hubei Province [2017CFB555]
- Foundation of Chinese Society of Clinical Oncology (CSCO) [Y-HS2019-39, Y-MX2016-048]
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Objective: To investigate the potential mechanism underlying the effect of lung carcinoma cell-derived exosomes on dendritic cell function. Materials and Methods: C57BL/6 (B6) mice were randomly divided into five groups: control, dendritic cell (DC), DC-NC, DC-siMALAT1, and siMALAT1. Tumor cell proliferation was measured by Ki-67 staining. LLC cells were divided into control, NC, and siMALAT1 groups, and exosomes secreted by each group were labeled as PEX, PEXN, and PEX-si, respectively. Exosomes and autophagic vacuoles were observed by transmission electron microscopy. MALAT1 expression in LLC, A549, and Beas-2b cells was examined by RT-PCR. The expression of IFN-gamma, IL-12, IL-10, and TGF-beta was observed by Elisa assay. Flow cytometry was used to observe the phagocytic function of DCs, costimulatory molecule expression, and T cell proliferation and differentiation. The protein expression of p-AKT, AKT, p-mTOR, mTOR, ALIX, TSG101, and CD63 was detected by Western blot. Results: Compared with Beas-2b cells, MALAT1 expression was significantly increased in both LLC and A549 cells and in their secreted exosomes, and LLC cells showed the highest expression of MALAT1 (P < 0.05). Tumor cell proliferation and tumor volume were significantly decreased in the siMALAT1 and DC-siMALAT1 groups compared to those in the control group. DC phagocytosis, inflammatory response, costimulatory molecule expression, and T cell proliferation in the siMALAT1 and PEX-si groups were significantly enhanced (P < 0.05), while DC autophagy and T cell differentiation were reduced (P < 0.05). The levels of p-AKT, AKT, p-mTOR, and mTOR in the PEX and PEXN groups were increased compared with those in the control group, while those in the siMALAT1 and PEXsi groups were significantly decreased (P < 0.05). Conclusion: Inhibition of MALAT1 expression in LLC-derived exosomes promoted DC function and T cell proliferation and suppressed DC autophagy and T cell differentiation, suggesting that MALAT1 inhibition may be a potential strategy for the clinical treatment of lung cancer.
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