Identification of REEP6 regulated genes and signaling pathways through RNA sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE271159 | GEO | 2024/11/20
REPOSITORIES: GEO
Similar Datasets
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:MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway. Total RNA was obtained from 40 pairs of OSCC patients with tumor specimens and their adjacent non-tumorous epithelia.
2015-01-07 | E-GEOD-45238 | biostudies-arrayexpress
Project description:Identification of REEP6 regulated genes and signaling pathways through RNA sequencing
| PRJNA1130362 | ENA
Project description:Aims: Oligoasthenozoospermia (OAS) causes male infertility. However, the etiology and pathogenesis of OAS are unclear, and specific therapy is lacking. Ferroptosis contributes to the progress of various diseases; however, its role in OAS is unknown. This study aimed to explore the mechanism of OAS and to find effective treatments. Results: Human OAS sperm exhibits biochemical and morphological hallmarks of ferroptosis. Ferroptosis represents a crucial role in OAS induced by cyclophosphamide (CP) of mice in vivo, and inhibiting ferroptosis can effectively improve OAS. Further search for safe, stable and clinically applicable of natural compounds found Salidroside （Sal）improved the sperm quality of OAS by attenuates ferroptosis-mediated lipid peroxidation in germ cells by increasing the expression of GPX4, and thus ameliorates OAS in vivo. To further investigate at which stage of spermatogenesis Sal acts, the result revealed that Sal increases the expression of GPX4 starting from primary spermatocytes gradually by immunohistochemistry. In vitro, we verified the above results in vivo using a mouse spermatocytes cell line, GC-2 cells. Mechanistically, integrated RNA-Seq and bioinformatic analysis showed that Sal likely promotes GPX4 expression by inhibiting NF-κB Pathway, thereby inhibiting ferroptosis. Innovation: Our findings support the view that ferroptosis plays an important role in patients with OAS, and provide convincing evidence that Sal ameliorates OAS by inhibiting ferroptosis-mediated lipid peroxidation via NF-κB pathway suppression. Conclusions: Thus, ferroptosis plays an important role in OAS, and Sal could ameliorate OAS by attenuating ferroptosis-mediated lipid peroxidation via NF-κB pathway inhibition.
2024-12-01 | GSE249162 | GEO
Project description:SMAD4 is a tumor suppressor mutated or silenced in multiple cancers including oral squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases and this loss correlated with worse progression free survival independent of other major clinical and pathological features. In a mouse model, Kras mutation induced benign papillomas while additional loss of Smad4 expression resulted in rapid development of invasive carcinoma. Examining regulatory pathways in organoids from SMAD4+ and SMAD4- mouse tumors, we found that either loss of SMAD4 or inhibition of TGFb signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC.
2024-05-14 | GSE228584 | GEO
Project description:Only a few studies have attempted to explore the potential role of FTO in gastric cancer, with one focusing on mitochondrial metabolism, while others have focused on the association of FTO with cell proliferation, migration, and invasion. To date, no study has comprehensively linked FTO-dependent m6A methylation to any form of cell death. We comprehensively explore the role of FTO-mediated m6A modification in gastric cancer ferroptosis by MeRIP-seq.
2024-03-03 | GSE210623 | GEO
Project description:Silica nanoparticles are a class of molecules commonly used in drug or gene delivery systems that either facilitate the delivery of therapeutics to specific drug targets or enable the efficient delivery of constructed gene products into biological systems. Some in vivo or in vitro studies have demonstrated the toxic effects of silica nanoparticles. Despite the availability of risk management tools in response to the growing use of synthetic silica in commercial products, the molecular mechanism of toxicity induced by silica nanoparticles is not well characterized. The purpose of this study was to elucidate the effects of silica nanoparticle exposure in three types of cells including human aortic endothelial cells, mouse-derived macrophages, and A549 non-small cell lung cancer cells using toxicogenomic analysis. The results indicated that among all three cell types, the TNF and MAPK signaling pathways were the common pathways upregulated by silica nanoparticles. These findings may provide insight into the effects of silica nanoparticle exposure in the human body and the possible mechanism of toxicity.
| S-EPMC7961477 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (OSCC) is a lethal digestive tract malignancy with limited effective interventions. This study aims to explore a new potential inhibitor on OSCC and investigate the underlying mechanisms. Based on a drug screen of an FDA-proven library consisting of 1404 compounds, we demonstrated that Omipalisib, a dual PI3K/mTOR inhibitor, markedly inhibited cell proliferation and colony formation in a panel of OSCC cell lines. Mechanistically, Omipalisib induced G0/G1 phase cell cycle arrest and apoptosis. Moreover, RNA-seq, KEGG and GSEA confirmed that the PI3K/mTOR signalling pathway is the primary target of Omipalisib in OSCC cells. Omipalisib treatment suppressed the PI3K/mTOR signalling pathway. Furthermore, Omipalisib exerted a significant antineoplastic effect on OSCC tumour xenografts in BALB/c nude mice without obvious side effects. The present study supports the rationale for using Omipalisib as a therapeutic approach for OSCC cases and suggests the potential clinical evaluation of this strategy.
2020-01-11 | GSE143462 | GEO
Project description:OSCC is a common cancer of the head and neck. Despite ongoing efforts, there remains a dearth of targeted drugs capable of effectively inhibiting OSCC growth. As the earliest discovered proto-oncogene in the SRSF family, targeted inhibition of SRSF1 plays an important role in tumor suppression. However, a comprehensive report on the expression, function, and mechanism of SRSF1 in OSCC has yet to be presented. This study retrospectively analyzed clinical samples from OSCC patients and discovered a significant correlation between the SRSF1 expression level and poor prognosis. In vitro experimentation demonstrated that SRSF1 knockdown inhibited OSCC growth, survival, lysosomal biogenesis and autophagy. To confirm the significance of lysosomal function and autophagy in the regulation of OSCC growth by SRSF1, cell rescue models were constructed. The aforementioned findings were subsequently validated in xenograft models. Ultimately, targeted knockdown of SRSF1 was found to significantly suppress OSCC growth by impeding lysosomal biogenesis and autophagy.
2023-12-01 | GSE244710 | GEO