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Lung Carcinoma Cells Secrete Exosomal MALAT1 to Inhibit Dendritic Cell Phagocytosis, Inflammatory Response, Costimulatory Molecule Expression and Promote Dendritic Cell Autophagy via AKT/mTOR Pathway

Authors
  • Liu, Yanyan1
  • Yin, Zhucheng2
  • Lu, Ping2
  • Ma, Yifei2
  • Luo, Bo2
  • Xiang, Lanxin3
  • Zhang, Wangli3
  • He, Yu4
  • Liang, Xinjun2
  • 1 Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
  • 2 Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
  • 3 Huazhong Agricultural University, Wuhan, Hubei
  • 4 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
Type
Published Article
Journal
OncoTargets and Therapy
Publisher
Dove Medical Press
Publication Date
Oct 20, 2020
Volume
13
Pages
10693–10705
Identifiers
DOI: 10.2147/OTT.S256669
PMID: 33116646
PMCID: PMC7586126
Source
PubMed Central
Keywords
License
Green

Abstract

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 si-MALAT1 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-γ, IL-12, IL-10, and TGF-β 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 PEX-si 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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