Similar Datasets
Project description:Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed 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 assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.
| S-EPMC8516910 | biostudies-literature
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:DLEU1 promotes oral squamous cell carcinoma progression through activating interferon-stimulated genes
| PRJNA739720 | ENA
Project description:DLEU1 promotes oral squamous cell carcinoma progression through activating interferon-stimulated genes [microarray]
| PRJNA739714 | ENA
Project description:DLEU1 promotes oral squamous cell carcinoma progression through activating interferon-stimulated genes [ChIP-Seq]
| PRJNA739721 | ENA
Project description:Autophagy is related to many cellular mechanisms and dysregulation of autophagy involves the pathological process in cancer. miR-10b activates autophagy, which promotes invasion and migration of OSCC. Its functional role in the mechanism of OSCC to autophagy remains to be unclear. Overexpression of miR-10b was followed by enhanced OSCC invasion and migration and activated autophagic protein, such as LC3II/ATG5. MiR-10b attracted Bim directly according to the Bio-informatics analyses and double luciferases reporter assays. Functional experiments further revealed that miR-10b could promote invasion and migration in vitro. In addition, miR-10b induced autophagy via inhibiting Bim in invasion and migration of OSCC. Notably, animal experiments confirmed that miR-10b-Bim promoted proliferation and autophagy in OSCC. In addition, this study provides a theoretical support for regulating the mechanism of OSCC by inducing autophagy with miR-10b-Bim as a target.
| S-EPMC9411559 | biostudies-literature
Project description:Metabolic abnormality is the major feature of laryngeal squamous cell carcinoma (LSCC), however, the underlying mechanism remain largely elusive. Fatty acid desaturase 1 (FADS1), as the key rate-limiting enzyme of polyunsaturated fatty acids (PUFAs), catalyzes dihomo-gamma-linolenic acid (DGLA) to arachidonic acid (AA). In this study, we reported that the expression of FADS1 was upregulated in LSCC, high FADS1 expression was closely associated with the advanced clinical features and poor prognosis of the recurrent LSCC patients after chemotherapy. Liquid chromatograph-mass spectrometry (LC-MS) analysis revealed that FADS1 overexpression induced greater conversion of DGLA to AA, suggesting an increased activity of FADS1. Similarly, the level of prostaglandin E2 (PGE2), a downstream metabolite of AA, was also elevated in cancerous laryngeal tissues. Functional assays showed that FADS1 knockdown suppressed the proliferation, migration and invasion of LSCC cells, while FADS1 overexpression had the opposite effects. Bioinformatic analysis based on microarray data found that FADS1 could activate AKT/mTOR signaling. This hypothesis was further validated by both in vivo and in vitro assays. Hence, our data has supported the viewpoint that FADS1 is a potential promoter in LSCC progression, and has laid the foundation for further functional research on the PUFA dietary supplementation interventions targeting FADS1/AKT/mTOR pathway for LSCC prevention and treatment.
| S-EPMC7181692 | biostudies-literature
Project description:BackgroundThe relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs.MethodsWe analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression.ResultsLPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemistry showed significantly (p<0.05) elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis. In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05); cellular migration was inhibited compared with control cells. Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression.ConclusionLPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration. LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.
| S-EPMC4372572 | biostudies-literature
Project description:Aerobic glycolysis is the main pathway for energy metabolism in cancer cells. It provides energy and biosynthetic substances for tumor progression and metastasis by increasing lactate production. Lactate dehydrogenase A (LDHA) promotes glycolysis process by catalyzing the conversion of pyruvate to lactate. Despite LDHA exhibiting carcinogenesis in various cancers, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study demonstrated that LDHA was over-expressed in both OSCC tissues and cell lines, and was significantly associated with lower overall survival rates in patients with OSCC. Using weighted gene correlation network analysis and gene set enrichment analysis for the gene expression data of patients with OSCC (obtained from The Cancer Genome Atlas database), a close association was identified between epithelial-mesenchymal transition (EMT) and LDHA in promoting OSCC progression. The knockdown of LDHA suppressed EMT, cell proliferation, and migration and invasion of OSCC cells in vitro. Moreover, the silencing of LDHA inhibited tumor growth in vivo. Oxamate, as a competitive LDHA inhibitor, was also suppressed diverse malignant biocharacteristics of OSCC cells. Our findings reveal that LDHA acts as an oncogene to promote malignant progression of OSCC by facilitating glycolysis and EMT, and LDHA may be a potential anticancer therapeutic target.
| S-EPMC6930919 | biostudies-literature