<p>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</p>

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 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.

A Low Albumin-to-Globulin Ratio Predicts a Poor Prognosis in Patients With Metastatic Non-small-cell Lung Cancer

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Extracellular Vesicle (EVs) Associated Non-Coding RNAs in Lung Cancer and Therapeutics

“…Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was the first lncRNA shown to be implicated in lung cancer metastasis [ 119 ]. Subsequently, Zhang and colleagues discovered that exosomal MALAT1 was substantially abundant in the serum of NSCLC patients, which sped up tumor migration and proliferation by inhibiting cell apoptosis and shortening cell cycle [ 120 ]. According to this research, exosomal MALAT1 may function as a non-invasive biomarker for the diagnosis of NSCLC or as a prospective therapeutic target for NSCLC ( Table 2 ) [ 121 ].…”

Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

“…Although the importance of autophagy and exosomes in tumor progression is well-documented ( Yu et al, 2007 ; Clayton et al, 2008 ; Skog et al, 2008 ; Hong et al, 2009 ; Svensson et al, 2013 ; Keulers et al, 2016 ; Ahmadi and Rezaie, 2020 ; Amaravadi et al, 2020 ), in recent years the understanding of their connection and interplay in cancer has aroused a lot of interest ( Table 1 ; Kulshreshtha et al, 2007 ; Bellot et al, 2009 ; Chiavarina et al, 2010 ; Mazure and Pouysségur, 2010 ; White et al, 2010 ; Aga et al, 2014 ; Dutta et al, 2014 ; Li et al, 2016 ; Zhang et al, 2018 , 2019 ; Jin et al, 2019 ; Meng et al, 2019 ; Shao et al, 2019 ; Wang et al, 2019 , 2020 ; Yeon et al, 2019 ; Yuwen et al, 2019 ; Zeng et al, 2019 ; Zhou et al, 2019 ; Dai et al, 2020 ; Han et al, 2020 ; Huang et al, 2020 ; Kulkarni et al, 2020 ; Kumar and Deep, 2020 ; Liu et al, 2020 ; Sung et al, 2020 ; Wu X. et al, 2020 ; Yao et al, 2020 ).…”