Transcriptome analysis of knockdown NUP210 in Huh7 hepatocyte-derived carcinoma cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE154486 | GEO | 2023/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome analysis of knockdown NUP210 in Huh7 hepatocyte-derived carcinoma cell line
| PRJNA646466 | ENA
Project description:Mechanical signals from the extracellular microenvironment have been shown to promote tumor and metastasis progression. It remains unclear how these signals are transmitted to the nucleus to regulate gene expression necessary for metastatic progression. In a genome-wide screen for metastasis-associated polymorphism in the non-coding regulatory region of the genome, we found NUP210, a nuclear pore complex protein as a metastasis susceptibility gene and a cellular mechanosensor. Depletion of NUP210 in metastatic cancer cells significantly reduces lung metastasis in mouse orthotopic transplantation models. Mechanistically, NUP210 interacts with histone H3.1/3.2 (preferentially enriched at the poised/bivalent gene promoters) at the nuclear periphery. To investigate how NUP210 regulates metastasis, we performed combined ChIP-seq and RNA-seq analysis to identify the NUP210-dependent downstream signaling pathways necessary for metastatic progression. Interestingly, RNA-seq analysis revealed that the loss of NUP210 in cancer cells significantly decreased the expression of mechanosensitive, cell adhesion/migration-related pro-metastatic genes. ChIP-seq analysis of H3K4me3 (transcriptional activation mark) and H3K27me3 (transcriptionally repressive, heterochromatin mark) in NUP210 WT/KO cells revealed that NUP210 loss resulted in increased heterochromatinization of mechanosensitive, cell migration-related genes associated at the nuclear periphery. Our results provide a new insight into the role of nuclear pore protein in regulating cellular mechanosensation and metastasis.
2021-03-05 | GSE146591 | GEO
Project description:We used microarrays to identify the genome-wide changes in gene expression of post-mitotic muscle cells when Nup210 is depleted
2017-06-02 | GSE98318 | GEO
Project description:This study delineated the downstream activity of oncogenic SMARCB1 and evaluated the genome-wide change of H3K27ac on chromatin.
2021-11-01 | GSE122727 | GEO
Project description:Hepatocellular carcinoma (HCC) is an aggressive, chemo resistant neoplasm with poor prognosis and limited treatment options. Exploring activated pathways upon drug treatment can be used to discover more effective anticancer agents to overcome therapy resistance and enhance therapeutic outcomes for patients with advanced HCC. Human tumor-derived cell lines recapitulate HCC diversity and are widely used for studying mechanisms that drive drug resistance in HCC. In this study, we show that regorafenib treatment activates Wnt/β-catenin signaling only in hepatoblast-like HCC cell lines and induces enrichment of markers associated with hepatic stem/progenitor cells. Moreover, activation of Wnt/β-catenin signaling via Wnt3a/R-Spo1 treatment protects these cells from regorafenib induced apoptosis. On the other hand, regorafenib resistant cells established by long-term regorafenib treatment demonstrate diminished Wnt/β-catenin signaling activity while TGF-β signaling activity of these cells is significantly enhanced. Regorafenib resistant cells (RRCs) also show increased expression of several mesenchymal genes along with an induction of CD24 and CD133 cancer stem cell markers. Moreover, regorafenib resistant cells also exhibit significantly augmented in vitro and in vivo migration capacity which could be reversed by TGF-β type 1 receptor (TGFb -R1) inhibition. When combined with regorafenib treatment, TGFβ-R1 inhibition also significantly decreased colony formation ability and augmented cell death in resistant spheroids. Importantly, when we knocked down TGFβ-R1 using a lentiviral plasmid, regorafenib resistant cells entered senescence indicating that this pathway is important for their survival. Treatment of RRCs with TGFβ-R1 inhibitor and regorafenib significantly abolished pSTAT3, pSMAD2 and pERK (44/42) expression suggesting the involvement of both canonical and non-canonical pathways. In conclusion, our data suggest that HCC tumors with aberrant activation in the Wnt/β-catenin pathway, might have higher intrinsic regorafenib resistance and the inhibition of this pathway along with regorafenib administration might increase regorafenib-induced cell death in combinational therapies. However, to resolve acquired regorafenib resistance developed in HCC patients, the combined use of TGF-β pathway inhibitors and Regorafenib constitute a promising approach that can increase regorafenib sensitization and prevent tumor recurrence.
| S-EPMC8386122 | biostudies-literature
Project description:It has been confirmed that nsun2 promotes cell proliferation and migration in hypopharyngeal cancer cell lines, but the pathway of nsun2 in hypopharyngeal cancer cell lines is poorly understood. We constructed stable cell lines by knocking down nsun2 to find the key genes of downstream pathway, and compared them with normal FaDu cell lines.It has been confirmed that nsun2 promotes cell proliferation and migration in FaDu cell line, but the pathway of nsun2 in FaDu cell line is poorly understood. We constructed stable cell lines by knocking down nsun2 to find the key genes of downstream pathway, compared them with normal FaDu cell lines.
2024-01-15 | GSE164886 | GEO
Project description:Analysis of Huh7 hepatocellular carcinoma (HCC) cells depleted for potassium channel KCa3.1, the intermediate conductance calcium-activated potassium channel. Result provide insight into the role of KCa3.1 in the carcinogenesis of HCC. We used microarrays to detail the gene expression differences between KCa3.1 knockdown and negative control in Huh7 HCC cells.
2018-06-23 | GSE116183 | GEO
Project description:BackgroundMEIS1 (Myeloid ecotropic viral integration site 1), as a homeobox (HOX) transcription factor, has a dual function in different types of cancer. Although numerous roles are proposed for MEIS1 in differentiation, stem cell function, gastrointestinal development and tumorigenesis, the involved molecular mechanisms are poor understood. Our aim in this study was to elucidate the functional correlation between MEIS1, as regulator of differentiation process, and the involved genes in cell differentiation in human esophageal squamous carcinoma (ESC) cell line KYSE-30.MethodsThe KYSE-30 cells were transduced using recombinant retroviral particles containing specific shRNA sequence against MEIS1 to knockdown MEIS1 gene expression. Following RNA extraction and cDNA synthesis, mRNA expression of MEIS1 and the selected genes including TWIST1, EGF, CDX2, and KRT4 was examined using relative comparative real-time PCR.ResultsRetroviral transduction caused a significant underexpression of MEIS1 in GFP-hMEIS1 compared to control GFP cells approximately 5.5-fold. While knockdown of MEIS1 expression caused a significant decrease in EGF and TWIST1 mRNA expression, nearly -8- and -12-fold respectively, it caused a significant increase in mRNA expression of differentiation markers including KRT4 and CDX2, approximately 34- and 1.14-fold, correspondingly.ConclusionMEIS1 gene silencing in KYSE-30 cells increased expression of epithelial markers and decreased expression of epithelial-mesenchymal transition (EMT) marker TWIST1. It may highlight the role of MEIS1 in differentiation process of KYSE-30 cells. These results may confirm that MEIS1 silencing promotes differentiation and decreases EMT capability of ESC cell line KYSE-30.
| S-EPMC6625128 | biostudies-literature
Project description:Regulation of downstream pathway of NSUN2 knockdown in hypopharyngeal carcinoma FaDu cell line
| PRJNA692368 | ENA
Project description:Neural stem cells (NSCs) are valuable for both basic research and clinical application. We previously reported a chemical cocktail that could reprogram somatic cells into neural progenitor cells. However, the process of chemical induction is complex and the underlying mechanism remains largely elusive. Here, we identified a new culture condition that greatly promotes the efficiency of NSC generation directly from mouse fibroblasts based on our reported chemical cocktail. Transcriptome and epigenome analyses during the reprogramming process demonstrated that growth factors including IL6, FGF5 and LIF were dynamically activated and contributed to the chemical cocktail induced cell fate changes. Interestingly, fibroblast-to-NSC conversion requires the synergistic action of these growth factors. Moreover, the reprogramming capacity of both chemical cocktail and growth factors require nucleoporin Nup210 to activate endogenous neural transcription factors SoxB1 family to initiate NSC fate. Our study not only provides a novel protocol to generate NSC directly from mouse fibroblasts, but also reveals an important role of growth factors in chemical-induced cellular reprogramming.
2019-12-31 | GSE108300 | GEO