Human
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA427233 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lung cancer is one of the most common cancers in the world, which accounts for about 27% of all cancer deaths. However, the mechanisms underlying the pathogenesis of lung cancer cells remain largely elusive. In this study, we examined the role of the Forkhead box protein P1 (FOXP1) in lung cancer development. Our Oncomine analysis shows that FOXP1 is downregulated in lung adenocarcinoma compared with normal lung tissue. Knockdown of FOXP1 promotes the proliferation growth and invasion of PC9 and A549 cells by regulating genes of chemokine signaling molecules, including CCR1, ADCY5, GNG7, VAV3, and PLCB1. Simultaneous knockdown of CCR1 and FOXP1 attenuated FOXP1 knockdown-induced increase of lung cancer cell growth. Finally, knockdown of FOXP1 in PC9 cells promotes the tumorigenesis via CCR1 signaling in xenograft mouse model. Taken together, our data suggest that FOXP1 plays important roles in preventing lung adenocarcinoma development via suppressing chemokine signaling pathways. Novel strategies might be developed to prevent the development of lung adenocarcinoma by targeting FOXP1
2018-02-10 | GSE108500 | GEO
Project description:Knockdown of FOXP1 promotes the development of lung adenocarcinoma
| PRJNA427471 | ENA
Project description:Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown. We propose to determine the roles for Foxp1/4 in lung development by deleting these genes in lung epithelial specific knockout mice. To explore the genome wide consequences of Foxp1/4 deficiency on secretory epithelial differentiation in the lung, we performed microarray analysis of Shh- cre control and Foxp1/4ShhcreDKO mutants lungs at E14.5, 3 embryos, respectively.
2012-08-01 | E-GEOD-34584 | biostudies-arrayexpress
Project description:Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown. We propose to determine the roles for Foxp1/4 in lung development by deleting these genes in lung epithelial specific knockout mice.
2012-08-02 | GSE34584 | GEO
Project description:Lung cancer is the leading cause of cancer-related death worldwide. KRAS mutations are the most common oncogenic alterations found in lung cancer. Unfortunately, treating KRAS-mutant lung adenocarcinoma (ADC) remains a major challenge in cancer treatment of directly inhibiting the KRAS oncoprotein, indicating the need for understanding the regulatory mechanism with this molecular profile. Here, we used both autochthonous and transplantable KRAS mutant tumor models to investigate the role of tumor-derived CUL4B in KRAS-driven lung cancers. We show that knockout or knockdown of CUL4B promotes lung adenocarcinoma growth and progression in both two models. Mechanistically, CUL4B directly binds to the promoter of Cxcl2 and epigenetically represses its transcription. CUL4B deletion increases the expression of CXCL2, which binds to CXCR2 on myeloid-derived suppressor cells (MDSCs) and promotes their migration to the tumor microenvironment, and in turn, suppresses anti-tumor immunity. Targeting MDSCs with anti-Gr-1 neutralizing antibody or treatment with CXCR2 antagonist SB265610 significantly suppresses MDSCs infiltration and delayed the growth of CUL4B knockdown KRAS mutant lung adenocarcinoma tumors. Moreover, a negative correlation between CUL4B and CXCL2 expression was observed in high-stage KRAS mutant lung ADC patients. Collectively, our study provides mechanistic insights into the novel tumor suppressor-like functions of CUL4B in regulating the KRAS-driven lung tumor development.
2026-01-15 | GSE222940 | GEO
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
2024-09-02 | BIOMD0000000827 | BioModels
Project description:The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To better understand how genomic alterations of NKX2-1 drive tumorigenesis, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma, and analyzed DNA binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation from NKX2-1-amplified human lung adenocarcinoma cell lines. Combining these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1, in addition to consensus binding motifs including a nuclear hormone receptor signature and a Forkhead box motif in NKX2-1-bound sequences. RNA interference analysis of NKX2-1-amplified cells compared to non-amplified cells demonstrated that LMO3 mediates cell proliferation downstream of NKX2-1; cistromic analysis that NKX2-1 may cooperate with FOXA1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transducer of lineage specific cell survival of NKX2-1-amplified lung adenocarcinomas. NKX2-1 ChIP-seq from three lung adenocarcinoma cell lines with amplification of NKX2-1
2013-01-22 | E-GEOD-39998 | biostudies-arrayexpress
Project description:MUC5AC is a secretory type of mucin, which is significantly overexpressed in lung adenocarcinoma and associated with poor survival outcomes. Expression of MUC5AC and its sialylation is required for alteration of tumor matrix remodeling through interacting with integrin β4 in lung adenocarcinoma. We have previously shown that sialylated MUC5AC is required for lung adenocarcinoma cell growth and metastasis. To understand the molecular mechanism of MUC5AC in lung adenocarcinoma development, we performed RNA sequence analysis using MUC5AC knockdown cells (A549-shMUC5AC) and scramble cells (A549-shRNA). We observed that several tumor matrix proteins including VCAN and integrin β4 were significantly downregulated and are associated with tumor angiogenesis. In this study, we reported that sialylated MUC5AC induces tumor angiogenesis by altering tumor matrix protein VCAN during lung adenocarcinoma development and metastasis.
2025-04-15 | GSE290456 | GEO
Project description:gefitinib-resistant lung adenocarcinoma cell lines（PC9/GR）transfect HUMT-specific shHUMT to knockdown HUMT1 and analysis differential gefitinib-resistant lung adenocarcinoma cell lines（PC9/GR）transfect HUMT-specific shHUMT to knockdown HUMT1 and analysis differential
2021-07-06 | GSE179146 | GEO