Effects of DLEU1 knockdown on gene expression profiles in oral squamous cell carcinoma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108851 | GEO | 2018/09/23
REPOSITORIES: GEO
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Project description:Long noncoding RNAs (lncRNAs) are deeply involved in cancer development, and we have previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is frequently overexpressed in oral squamous cell carcinoma (OSCC) cells, where it plays an oncogenic role. In this study, we aimed to further clarify the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that knockdown of DLEU1 induced substantial changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, depletion of DLEU1 significantly downregulated levels of H3K4me3/H3K27ac and expression of a number of interferon-stimulated genes (ISGs) including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assay suggested that DLEU1 upregulates ISGs through activating the JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, is frequently overexpressed in primary OSCC tumors, and knockdown of IFITM1 attenuated OSCC cell proliferation, migration and invasion. Our data suggest that DLEU1 exerts its oncogenic function through, at least in part, activating a series ISGs in OSCC cells.
2021-09-12 | GSE178608 | GEO
Project description:Long noncoding RNAs (lncRNAs) are deeply involved in cancer development, and we have previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is frequently overexpressed in oral squamous cell carcinoma (OSCC) cells, where it plays an oncogenic role. In this study, we aimed to further clarify the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that knockdown of DLEU1 induced substantial changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, depletion of DLEU1 significantly downregulated levels of H3K4me3/H3K27ac and expression of a number of interferon-stimulated genes (ISGs) including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assay suggested that DLEU1 upregulates ISGs through activating the JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, is frequently overexpressed in primary OSCC tumors, and knockdown of IFITM1 attenuated OSCC cell proliferation, migration and invasion. Our data suggest that DLEU1 exerts its oncogenic function through, at least in part, activating a series ISGs in OSCC cells.
2021-09-12 | GSE178611 | GEO
Project description:Comparison of gene expression profiling between DLEU1 downregulated Raji BL cell and wild type Raji BL cell Transcription Activator-Like Effector Nucleases (TALENs) mediated DLEU1 downregulated Raji burkitt lymphoma (BL) cell clone and wild type (control) Raji cell clone were analyzed in duplicate. Four samples were hybridized to HGU133_plus_2 Genechip(Affymetrix) and scanned with the Scanner 3000 7G.
2015-06-04 | E-GEOD-65674 | biostudies-arrayexpress
Project description:Comparison of gene expression profiling between DLEU1 downregulated Raji BL cell and wild type Raji BL cell
2015-06-04 | GSE65674 | GEO
Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high-density single-nucleotide polymorphism array analysis and genome-wide gene expression profiling on OSCC tumors. These analyses identified "absent in melanoma (AIM2)" and "interferon-inducible gene 16 (IFI16)," mapped to the hematopoietic IFN-inducible nuclear proteins with 200-amino acid repeat (HIN-200) gene cluster in the amplified region of chromosome 1q23, with overexpression in OSCCs. AIM2 and IFI16 are cytoplasmic double-stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells resulted in the suppression of cell growth and the induction of apoptosis, accompanied by the downregulation of NF-κB activation. Because all of the OSCC cell lines had impairment of p53 activity, wild-type p53 was introduced in p53-deficient OSCC cells, and as a result, the expression of wild-type p53 suppressed cell growth and induced apoptosis via suppression of NF-κB activity. Finally, the coexpression of AIM2 and IFI16 significantly enhanced cell growth in p53-deficient cells; in contrast, the expression of AIM2 and/or IFI16 in cells bearing wild-type p53 suppressed cell growth. Moreover, AIM2 and IFI16 synergistically enhanced NF-κB signaling in p53-deficient cells. Thus, expression of AIM2 and IFI16 may have oncogenic functions in OSCC cells inactivating p53 system. Copy number analysis of Affymetrix 250K SNP arrays was performed for 5 oral leukoplakia samples, 20 oral squamous cell carcinoma samples, and 8 oral squamous cell carcinoma cell lines.
2011-12-30 | E-GEOD-34507 | biostudies-arrayexpress
Project description:Effects of DLEU1 knockdown on gene expression profiles in oral squamous cell carcinoma cells
| PRJNA428943 | ENA
Project description:As a Class II small leucine-rich proteoglycan, fibromodulin (FMOD) plays critical roles in collagen fibrillogenesis and angiogenesis. However, the biological function of FMOD in oral squamous cell carcinoma remains unknown to date. In this study, immunohistochemistry and immunofluorescence assays identified that FMOD protein was located in cytoplasm and nucleus and was overexpressed in OSCC tissues and cell lines. Clinical analysis confirmed that FMOD overexpression showed a significant association with malignant progression (P=0.011) and lymph node metastasis (P=0.032) in OSCC patients. Moreover, loss-of-function studies verified that knockdown of FMOD significantly inhibited OSCC growth and metastasis in vitro and in vivo. Mechanismly, RNA sequencing studies further confirmed that. Knockdown of FMOD expression inhibited OSCC cell proliferation, migration, invasion, and tumor growth probably through altering transcriptome leading to active cell cycle, down-regulating Cell adhesion molecules and ECM-receptor interaction and through inhibiting EGFR-ERK and EGFR-AKT pathways.
2023-08-31 | GSE227643 | GEO
Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high-density single-nucleotide polymorphism array analysis and genome-wide gene expression profiling on OSCC tumors. These analyses identified "absent in melanoma (AIM2)" and "interferon-inducible gene 16 (IFI16)," mapped to the hematopoietic IFN-inducible nuclear proteins with 200-amino acid repeat (HIN-200) gene cluster in the amplified region of chromosome 1q23, with overexpression in OSCCs. AIM2 and IFI16 are cytoplasmic double-stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells resulted in the suppression of cell growth and the induction of apoptosis, accompanied by the downregulation of NF-κB activation. Because all of the OSCC cell lines had impairment of p53 activity, wild-type p53 was introduced in p53-deficient OSCC cells, and as a result, the expression of wild-type p53 suppressed cell growth and induced apoptosis via suppression of NF-κB activity. Finally, the coexpression of AIM2 and IFI16 significantly enhanced cell growth in p53-deficient cells; in contrast, the expression of AIM2 and/or IFI16 in cells bearing wild-type p53 suppressed cell growth. Moreover, AIM2 and IFI16 synergistically enhanced NF-κB signaling in p53-deficient cells. Thus, expression of AIM2 and IFI16 may have oncogenic functions in OSCC cells inactivating p53 system.
2011-12-30 | GSE34507 | GEO
Project description:Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. Conclusions: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.
2023-01-10 | GSE222429 | GEO
Project description:Oral squamous cell carcinoma (OSCC) develop multi-step carcinogenesis, including the concept of the field cancerization. DEK gene is considered to be a proto-oncogene, has multifaceted functions, such as replication, transcription, and chromatin remodeling, and also affects oncogenic process, such as cellular proliferation, differentiation, senescence, and apoptosis. DEK overexpression has proposed to be closely associated with many malignancies, however, functional mechanisms and crucial roles are still unclear. DEK-expressing cells significantly increased in human oral squamous cell carcinogenesis. We generated ubiquitous and squamous cell-specific Doxycycline (DOX)- inducible Dek mice (iDek and iDek-e mice, respectively). DOX administrated (DOX+) iDek mice promoted field cancerization and the development of OSCC in the environment exposed to carcinogen. By the microarray expression profiling analysis, the promotion of the filed cancerization by Dek overexpression was mediated by the upregulation of DNA replication- and cell cycle (G1 to S phase transition)-related genes. Further, Dek-overexpressed tongue tumors were progressed by proliferating cell nuclear antigen (Pcna) and the elongator complex protein 3 (Elp3). Our data suggest that, by DEK overexpression enhances the carcinogenesis, including field cancerization, of OSCC stimulating the G1-to-S phase transition in the cell-cycle and DNA replication, even after carcinogen-exposed environment, and offers a fascinating target for treatment and prevention of OSCC.
2016-10-05 | GSE87587 | GEO