Identification of differentially expressed genes using microarray analysis and COL6A1 induction of bone metastasis in non-small cell lung cancer
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PROVIDER: PRJNA733050 | ENA |
REPOSITORIES: ENA
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Project description:Non-small cell lung cancer (NSCLC) is a major cause of cancer-associated mortality worldwide, and bone metastasis is the most prevalent event observed in patients with advanced NSCLC. However, the pathogenesis of bone metastases has not been fully elucidated. In the present study, differentially expressed genes (DEGs) were identified by gene expression microarray analysis of NSCLC tissue samples with or without bone metastases. Subsequently, collagen family collagen 6A1 (COL6A1) was chosen as the target gene through Ingenuity Pathway Analysis and reverse transcription-quantitative (RT-q)PCR validation of the top eight DEGs. COL6A1 was overexpressed or knocked down, and the proliferation and invasion of NSCLC cells was assessed using Cell Counting Kit-8, colony formation and Transwell invasion assays. Additionally, the osteogenic capacity of HOB and hES-MP 002.5 cells was assessed using RT-qPCR, western blotting, Alizarin Red staining and alkaline phosphatase staining. A total of 364 DEGs were identified in NSCLC tissues with bone metastases compared with NSCLC tissues without bone metastases, including 140 upregulated genes and 224 downregulated genes. Gene Ontology analysis indicated that the upregulated and downregulated genes were primarily enriched in ‘cellular process’, ‘metabolic process’ and ‘biological regulation’. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the upregulated genes were primarily enriched in ‘cysteine and methionine metabolism’, ‘oxidative phosphorylation’ and the ‘ribosome’, while the downregulated genes were primarily enriched in ‘transcriptional mis-regulation in cancer’, ‘ribosome’ and ‘mitophagy in animals’. COL6A1 was highly expressed in NSCLC tissue samples with bone metastases. Functionally, COL6A1 overexpression induced the proliferation and invasion of HARA cells, and knockdown prevented the proliferation and invasion of HARA-B4 cells. Finally, it was demonstrated that HOB and hES-MP 002.5 cells exhibited osteogenic capacity, and overexpression of COL6A1 in HARA cells increased adhesion of these cells to the osteoblasts, whereas knockdown of COL6A1 in HARA-B4 cells reduced their adhesive ability. In conclusion, COL6A1 may serve as a potential diagnostic marker and therapeutic target for bone metastasis in NSCLC.
2021-08-18 | GSE175601 | GEO
Project description:Non-small cell lung cancer (NSCLC) is a major cause of cancer-associated mortality worldwide, and bone metastasis is the most prevalent event observed in patients with advanced NSCLC. However, the pathogenesis of bone metastases has not been fully elucidated. In the present study, differentially expressed genes (DEGs) were identified by gene expression microarray analysis of NSCLC tissue samples with or without bone metastases. Subsequently, collagen type 6A1 (COL6A1) was chosen as the target gene through Ingenuity Pathway Analysis and reverse transcription-quantitative (RT-q) PCR validation of the top eight DEGs. COL6A1 was overexpressed or knocked down, and the proliferation and invasion of NSCLC cells was assessed using Cell Counting Kit-8, colony formation and Transwell invasion assays. Additionally, the osteogenic capacity of HOB and hES-MP 002.5 cells was assessed using RT-qPCR, western blotting, Alizarin Red and alkaline phosphatase staining. A total of 364 DEGs were identified in NSCLC tissues with bone metastases compared with NSCLC tissues without bone metastases, including 140 upregulated and 224 downregulated genes. Gene Ontology analysis results demonstrated that the upregulated and downregulated genes were primarily enriched in 'cellular process', 'metabolic process' and 'biological regulation'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the upregulated genes were primarily enriched in 'cysteine and methionine metabolism', 'oxidative phosphorylation' and 'ribosome', whereas the downregulated genes were primarily enriched in the 'transcriptional misregulation in cancer', 'ribosome' and 'mitophagy-animal' pathways. COL6A1 was highly expressed in NSCLC tissue samples with bone metastases. Functionally, COL6A1 overexpression induced the proliferation and invasion of HARA cells, and its knockdown inhibited the proliferation and invasion of HARA-B4 cells. Finally, it was demonstrated that HOB and hES-MP 002.5 cells exhibited osteogenic capacity, and overexpression of COL6A1 in HARA cells increased the adhesion of these cells to the osteoblasts, whereas knockdown of COL6A1 in HARA-B4 cells reduced their adhesive ability. In conclusion, COL6A1 may serve as a potential diagnostic marker and therapeutic target for bone metastasis in NSCLC.
| S-EPMC8358737 | biostudies-literature
Project description:Collagen 6 (COL6) is known for its role in a spectrum of congenital muscular dystrophies, which are often accompanied by respiratory dysfunction. However, little is known regarding the function of COL6 in the lung. We confirmed the presence of COL6 throughout the basement membrane region of mouse lung tissue. We studied lung structure and organization in a previously described Col6a1-/- mouse, which do not produce detectable COL6 in the lung. The Col6a1-/- mouse displayed multiple histopathological alveolar and airway abnormalities. The airspaces of Col6a1-/- lungs appeared simplified, with larger (29%, p<0.01) and fewer (31%, p<0.001) alveoli. These airspace abnormalities included a reduction in IsolectinB4+ alveolar capillaries and Sftpc+ ATII cells. Alterations in lung function consistent with these histopathological changes were evident. Col6a1-/- mice also displayed multiple airway changes including increased branching (59%, p<0.001), increased mucosal thickness (34%, p<0.001) and increased epithelial cell density (13%, p<0.001). Comprehensive transcriptome analysis revealed loss of COL6 is associated with reductions in integrin-paxillin-PI3K signaling in vivo. In vitro, COL6 promoted steady-state phospho-paxillin levels and reduced cell density (16-28%, p<0.05) at confluence. Inhibition of PI3K, or its downstream effectors, resulted in increased cell density to a level similar to that seen on matrices lacking COL6.
2019-08-10 | GSE135667 | GEO
Project description:Understanding the molecular mechanisms and gene expression in laryngeal squamous cell carcinoma (LSCC) may explain its aggressive biological behavior and regional metastasis pathways. Better understanding of the molecular mechanisms underlying LSCC metastasis and the search for possible molecular targets seems promising. Interpreting the links between the differentially expressed genes in advanced stages can lead to a search for predictive markers that can also help determine the possible treatment routes. We designed this study to detect possible genetic alterations in a homogeneous group of patients with locoregionally advanced laryngeal cancer who underwent total laryngectomy and neck dissection. Patients with and without lymph node metastasis were selected to examine the differential gene expression in the normal mucosa, tumor, and lymph node tissues of each patient. Our main purpose was to identify the possible commonly expressed genes in this homogenous group of Turkish patients with locoregionally advanced laryngeal cancer. Second, we aimed to determine the predictive role of these genes in lymph node metastasis and overall prognosis.
2022-10-07 | GSE201777 | GEO
Project description:BackgroundOur objective was to examine how the gene expression profile of tumor tissue correlates with lymph node metastasis in patients with advanced colorectal adenocarcinoma (CRAC).MethodsWe studied 36 patients (20 men and 16 women, 22-90 years of age) treated for CRAC (classifications of T2, T3, or T4; histological grade of G1 or G2). Amplified tumor mRNA samples were exposed to 20,000 human sequence probes and digitized images of the hybridized samples were analyzed.ResultsOn average, 2389 probes were detected above the background, with an average correlation R value of 0.19 between data from different patient groups (with or without lymph node invasion, colon or rectal, with or without angio-lymphatic invasion, with or without recurrence). Lymph node metastasis had a statistically significant signature according to Significance Analysis of Microarrays (SAM) and parametric t-tests, with a false discovery rate (FDR)=0.1% and p=0.001, respectively. Cross-correlation of these two tests identified 102 transcripts as being potentially related to node metastases, with fold changes in the range of 2.182-12.960.ConclusionWe identified 102 differentially expressed genes related to the presence of lymph node metastases in patients with advanced colorectal cancer.
| S-EPMC3885480 | biostudies-literature
Project description:Differentially expressed genes related to lymph node metastasis in advanced laryngeal squamous cell cancers
| PRJNA833026 | ENA
Project description:Tumor metastasis continues to be the most significant contributor to cancer related mortality, and although several studies have examined expression profiles emanating from patients with metastatic disease, very little information is available about signatures that differentiate metastatic lesions from primary tumors and associated normal tissues, largely because such matched tissue sample series are rare. This study was specifically designed to identify the metastasis relevant microRNAs in colorectal cancer and characterize microRNAs that modulate the metastatic phenotype. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) with the accession number GSE54088, was generated including the basic analysis as contained in the manuscript published in Cancer Research with the PMID 26069251.
| S-EPMC4664671 | biostudies-literature
Project description:BackgroundOur study aimed to analyze differential microRNA expression between myelodysplastic syndromes (MDS) and normal bone marrow, and to identify novel microRNAs relevant to MDS pathogenesis.MethodsMiRNA microarray analysis was used to profile microRNA expression levels in MDS and normal bone marrow. Quantitative real-time polymerase chain reaction was employed to verify differentially expressed microRNAs.ResultsMiRNA microarray analysis showed 96 significantly upregulated (eg, miR-146a-5p, miR-151a-3p, miR-125b-5p) and 198 significantly downregulated (eg, miR-181a-2-3p, miR-124-3p, miR-550a-3p) microRNAs in MDS compared with normal bone marrow. The quantitative real-time polymerase chain reaction confirmed the microarray analysis: expression of six microRNAs (miR-155-5p, miR-146a-5p, miR-151a-3p, miR-221-3p, miR-125b-5p, and miR-10a-5p) was significantly higher in MDS, while 3 microRNAs (miR-181a-2-3p, miR-124-3p, and miR-550a-3p) were significantly downregulated in MDS. Bioinformatics analysis demonstrated that differentially expressed microRNAs might participate in MDS pathogenesis by regulating hematopoiesis, leukocyte migration, leukocyte apoptotic process, and hematopoietic cell lineage.ConclusionsOur study indicates that differentially expressed microRNAs might play a key role in MDS pathogenesis by regulating potential relevant functional and signaling pathways. Targeting these microRNAs may provide new treatment modalities for MDS.
| S-EPMC7337584 | biostudies-literature
Project description:ETS1 induction by the omental microenvironment promotes ovarian cancer metastasis
| PRJNA395678 | ENA