Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

M2 tumor-associated macrophage promoted DNA methylation in lung cancer metastasis via intensifying EZH2.

This study aimed to explore the interaction between the tumor-associated macrophage (TAM) and enhancer of zeste homolog 2 (EZH2) in tumor microenvironment of lung cancer are obscure. M2 type of TAM was induced by interleukin-4 (IL-4) and interleukin-13 (IL-13) in RAW264.7 cells. Subsequently, the co-culture system of the M2 RAW264.7 treating LLC-1 cells were constructed to evaluate the cell proliferation, migration and invasion abilities. On top of that, the M2 RAW264.7 was injected into the LLC-1 cells-bearing mice. Tumor growth and the number of metastatic nodes were observed. Moreover, DNA methylation, EZH2 expression, target genes of EZH2 and the M2 type TAM-related markers were detected in vivo and in vitro . Further experiments of EZH2 function in lung cancer were carried out by the addition of EZH2 inhibitor (GSK126) and si-EZH2. M2 type of TAM was induced with IL-4 and IL-13 with increased expression of CD206, CD68, CD163 and Arg1. Following co-culture with M2 type TAM, the proliferative, invasive, migrative abilities, tumor growth and metastasis, and the DNA methylation, EZH2 level were strengthened whereas the target genes of EZH2, including p21, CDKN2A, CDKN2B were reduced in LLC-1 cells and LLC-1 cell-bearing mice. Of note, GSK126 and si-EZH2 offset the M2 type TAM's effects, and inhibited the LLC-1 cell metastasis, DNA methylation and tumor growth. M2 type TAM promoted DNA methylation in LLC-1 cells and LLC-1 cell-bearing mice, which is related to the intensified EZH2.

A Meta-analysis of Randomised Controlled Trials Comparing Combination Therapy as Second-line Treatment With Monotherapy in Advanced Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR mutation; however, resistance is common. Combinatorial strategies have been explored to improve survival. This meta-analysis assesses the efficacy and safety of combination therapy versus monotherapy in patients with advanced NSCLC who failed first-line EGFR-tyrosine kinase inhibitor treatment. METHODS: We searched randomized controlled trials from PubMed, Web of Science, Google Scholar, Cochrane Library, and ClinicalTrial.gov. The efficacy and toxicity of combination treatment groups were assessed in terms of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: This meta-analysis included 6 randomized controlled trials covering 785 participants. The results showed that the combined regimen arm had no significant improvement of PFS (log hazard ratio = -0.228, 95% CI: -0.543 to 0.087, P = 0.157), ORR (odds ratio = 1.147 [95% CI: 0.577, 2.281], P = 0.695), DCR (odds ratio = 1.578 [95% CI: 0.428, 5.821], P = 0.493), and AEs, including fatigue and diarrhea (odds ratio = 0.833 [95% CI: 0.297, 2.333], P = 0.728 for fatigue and odds ratio = 2.268 [95% CI: 0.544, 9.448], P = 0.261 for diarrhea). CONCLUSIONS: Combination therapy may not provide a significant improvement in PFS, ORR, DCR, and incidence of AEs compared with monotherapy in patients with advanced NSCLC with EGFR mutations. Further research is needed to investigate the optimal sequencing of combination therapy in patients with NSCLC with different molecular targets to determine the most effective treatment strategy that can improve outcomes and quality of life for these patients.

MiRNA-144-5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells.

BACKGROUND: Lung adenocarcinoma (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144-5p targeting CDCA3 to inhibit LUAD proliferation. METHODS: MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis. TargetScan and miRTarBase databases were adopted to predict the target genes of miRNA, and the signaling pathways involved were analyzed by gene set enrichment analysis. The functions of LUAD cells were analyzed by CCK-8, colony formation assay, stem cell spheroidization assay, and flow cytometry. The expression levels of CDCA3, p53, and cell cycle-associated proteins were evaluated by Western blot. RESULTS: The expression of miRNA-144-5p was significantly down-regulated in LUAD, but overexpression of it repressed proliferation and spheroidization, and promoted apoptosis of LUAD cells. By bioinformatics prediction and dual-luciferase reporter assay, miRNA-144-5p was validated to target CDCA3, thereby regulating proliferation of LUAD cells. Besides, the results of cell experiments showed that miRNA-144-5p targeting CDCA3 affected cell proliferation and apoptosis in LUAD by regulating cell cycles, and miRNA-144-5p/CDCA3 mediated the p53 signaling pathway to affect the growth of LUAD cells. SIGNIFICANCE: Through the study of the pathogenesis of miRNA-144-5p regulating LUAD, we can better understand the molecular mechanism underlying LUAD development.

Microarray analysis of long non-coding RNA expression profiles in Marfan syndrome.

Long non-coding RNAs (lncRNAs) serve a crucial role in every aspect of cell biological functions as well as in a variety of diseases, including cardiovascular disease, cancer and nervous system disease. However, the differential expression profiles of lncRNAs in Marfan syndrome (MFS) have not been reported. The aim of the present study was to identify potential target genes behind the pathogenesis of MFS by analyzing microarray profiles of lncRNA in aortic tissues from individuals with MFS and normal aortas (NA). The differentially expressed lncRNA profiles between MFS (n=3) and NA (n=4) tissues were analyzed using microarrays. Bioinformatics analyses were used to further investigate the candidate lncRNAs. Reverse transcription-quantitative (RT-qPCR) was applied to validate the results. In total, the present study identified 294 lncRNAs (245 upregulated and 49 downregulated) and 644 mRNAs (455 upregulated and 189 downregulated) which were differential expressed between MFS and NA tissues (fold change ≥1.5; P<0.05). Gene Ontology enrichment analysis indicated that the differentially expressed mRNAs were involved in cell adhesion, elastic fiber assembly, extracellular matrix (ECM) organization, the response to virus and the inflammatory response. Kyoto Encyclopedia of Gene and Genomes pathway analysis indicated that the differentially expressed mRNAs were mainly associated with focal adhesion, the ECM-receptor interaction, the mitogen-activated protein kinase signaling pathway and the tumor necrosis factor signaling pathway. The lncRNA-mRNA coexpression network analysis further elucidated the interaction between the lncRNAs and mRNAs. A total of five lncRNAs (uc003jka.1, uc003jox.1, X-inactive specific transcript, linc-lysophosphatidic acid receptor 1 and linc-peptidylprolyl isomerase domain and WD repeat containing 1) with the highest degree of coexpression were selected and confirmed using RT-qPCR. In the present study, expression profiles of lncRNA and mRNA in MFS were revealed using microarray analysis. These results provided novel candidates for further investigation of the molecular mechanisms and effective targeted therapies for MFS.