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Exosomal miR-552-5p Regulates the Role of NK Cells in EMT of Gastric Cancer via the PD-1/PD-L1 Axis

Year: 2024

Type: article

Abstract: Background: While previous studies have established the role of exosomal miR-552-5p in promoting gastric cancer (GC) progression, the exact mechanisms through which it modulates the PD-1/PD-L1 axis to affect NK cell function and subsequently influence GC epithelial-mesenchymal transition (EMT) remain to be elucidated.Methods: Western blot, transmission electron microscopy (TEM), and nanoparticle tracking analysis were used to characterize exosomes that were isolated from GC cell supernatants.Subcutaneous AGS cell injections expressing either Lv-miR-552-5p or Lv-NC were administered to nude BALB/C mice.Mice received intraperitoneal injections of anti-PD-L1 antibody (12.5 mg/kg) or isotype control IgG weekly for two weeks.Flow cytometry assessed NK cell proportions and activation receptor (NKG2D, NKp46) and PD-L1 expression.ELISA measured cytokine levels (IFN-γ, granzyme B, perforin).Immunohistochemistry evaluated EMT marker expression in tumor tissues.An in vitro co-culture of NK cells with Exo-Lv-miR-552-5p or Exo-Lv-NC and GC cells was established.EMT protein expression in GC cells was analyzed by Western blot and immunofluorescence.Transwell assays and a tail vein-lung metastasis model in nude mice tested GC cell migration and invasion.Results: Expression of NKG2D, NKp46, and PD-L1 was significantly reduced in Exo-Lv-miR-552-5p mice peripheral blood NK cell percentage.Increased treatment with PD-L1 inhibitors reversed the considerable reduction in IFN-γ, granzyme B, and perforin cytokine expression levels.Exosomal miR-552-5p overexpression in NK cells reduced E-cadherin expression while increasing N-cadherin and vimentin expression in GC cells, promoting migratory and invasive properties.Conclusions: GC-derived exosomal miR-552-5p promotes EMT in GC by inhibiting NK cell activity via the PD-1/PD-L1 axis, which provides new insights into the role of exosomal miR-552-5p in GC progression and immune escape.

Source: Journal of Cancer

DOI: 10.7150/jca.102360

Authors: Jingwen Qin, Jinhua Yang, Haopeng Cui, Chunling Feng, Aiqun Liu

Institutions: Guangxi Medical University, Tumor Hospital of Guangxi Medical University

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337