HLA-DPA1 overexpression inhibits cancer progression, reduces resistance to cisplatin, and correlates with increased immune infiltration in lung adenocarcinoma.

PURPOSE: Human Leukocyte Antigen-DP alpha 1 (HLA-DPA1) is a critical gene in antigen-presenting cells and plays a significant role in immune regulation. The objective of this study was to comprehensively analyze the roles of HLA-DPA1 and its association with lung adenocarcinoma (LUAD). METHODS: We utilized bioinformatics and conducted a meta-analysis to examine the roles of HLA-DPA1 expression on the progression and immunity of LUAD. We also performed CCK-8, wound healing, and Transwell assays to validate the functions of HLA-DPA1 in LUAD. RESULTS: HLA-DPA1 expression is downregulated in LUAD tissues and is associated with gender, race, age, smoking history, clinical stage, histological type, lymph node metastasis, and prognosis of patients with LUAD. HLA-DPA1 is involved in immune responses, leukocyte cell-cell adhesion, and antigen processing and presentation. Overexpression of HLA-DPA1 inhibits cancer cell proliferation, migration, and invasion while promoting cell sensitivity to cisplatin in A549 and A549/DDP cells. Additionally, overexpression of HLA-DPA1 correlates with tumor purity, stromal, immune, and ESTIMATE scores, the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils), and immune cell markers (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, and cluster of differentiation 8A). CONCLUSIONS: Decreased HLA-DPA1 expression is associated with poor prognosis and immune infiltration in LUAD while HLA-DPA1 overexpression inhibits cancer cell proliferation and progression. Therefore, HLA-DPA1 shows potential as a prognostic biomarker and a therapeutic target for LUAD.

LncRNA NEAT1-miR-101-3p/miR-335-5p/miR-374a-3p/miR-628-5p-TRIM6 axis identified as the prognostic biomarker for lung adenocarcinoma via bioinformatics and meta-analysis.

BACKGROUND: Overexpression of the tripartite motif containing 6 (TRIM6) is associated with dismal prognosis in cancer patients, but its exact roles in lung adenocarcinoma (LUAD) have not been reported. METHODS: The roles of TRIM6 are identified by using The Cancer Genome Atlas (TCGA), TIMER2, Gene Expression Omnibus (GEO), etc., and the regulatory networks and related-prognostic biomarkers of TRIM6 are identified via the ENCORI and LNCAR databases in the LUAD progression. RESULTS: TRIM6 expression level in LUAD tissues was significantly increased. TRIM6 over-expression level in LUAD patients was associated with smoking, clinical stage, histological type, lymph node metastasis, TP53 mutation and dismal prognosis, and related to prognosis-related age, race, sex, clinical stage and tumor purity of LUAD patients. TRIM6 overexpression was associated with the levels of CD8+ T cells, macrophages, neutrophils and myeloid dendritic cells, and correlated with the levels of LUAD immune cell markers CD8A, IRF5, CD163, VSIG4, MS4A4A, ITGAM, HLA-DPA1, NRP1, ITGAX, etc. TRIM6 might influence the progression of LUAD by regulating homologous recombination, oocyte meiosis, and ubiquitin-mediated proteolysis. LUAD patients with overexpression of miR-101-3p, miR-335-5p, miR-374a-3p, miR-628-5p, and NEAT1 had a poor prognosis. CONCLUSIONS: NEAT1-miR-101-3p/335-5p/374a-3p/628-5p-TRIM6 network, which we constructed from our results, might be an important factor in the dismal prognosis of LUAD patients.

MiR-26a functions as a tumor suppressor in ambient particulate matter-bound metal-triggered lung cancer cell metastasis by targeting LIN28B-IL6-STAT3 axis.

Exposure to ambient particulate matter (PM) has been linked to the increasing incidence and mortality of lung cancer, but the principal toxic components and molecular mechanism remain to be further elucidated. In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 µg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion. In vivo pulmonary colonization assay further indicated that WE-PM10 enhanced the metastatic ability of A549 cells. In addition, luciferase reporter assay demonstrated that 3' untranslated region of LIN28B was a direct target of miR-26a. Last but not the least, the key toxic contribution of metals in WE-PM10 was confirmed by the finding that removal of metals through chelation significantly rescued WE-PM10-mediated inflammatory, carcinogenic and metastatic responses. Taken together, miR-26a could act as the tumor suppressor in PM10-related lung cancer, and PM10-bound metals promoted lung cancer cell metastasis through downregulation of miR-26a that directly mediated LIN28B expression.