Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267510 | ENA |
REPOSITORIES: ENA
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Project description:mathematical model, with accompanying quantitative experimental data, for binding and trafficking properties of the epidermal growth factor (EGF) receptor on B82 fibroblasts, and propose a theoretical dependence of cell proliferation rate on these properties. Model encoded by Matthieu Maire adn submitted to BioModels by Krishna Kumar Tiwari.
2020-03-19 | MODEL2003190005 | BioModels
Project description:Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. The G1 to S phase (G1/S) transition is the key step that drives cell to the division cycle, and its dysregulation contributes to unrestrained cell proliferation and consequent tumor development.In this study, we examined lncRNA expression profiles during cell cycle using serum starvation-stimulation model in human skin fibroblasts (SFs) and identified that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1 phase and in hepatocellular carcinoma (HCC) tissues. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor growth. Up-regulation of SNHG17 was correlated with high c-Myc level in human HCC. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc up-regulation, G1/S transition and cell proliferation. And the proliferation-stimulatory effect of SNHG17 was abrogated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the ubiquitylated c-Myc level and reduced c-Myc stability, suggesting that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which provide potential targets for cancer therapy.
2021-02-10 | GSE166448 | GEO
Project description:The purpose of this study was to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.
| 2348989 | ecrin-mdr-crc
Project description:Centromere protein F (CENPF), a mitosis-related protein, is overexpressed in hepatocellular carcinoma (HCC) and has emerged as a promising biomarker for early HCC. However, with ultra-large molecular weight of 358kDa of CENPF, no study has directly explored its carcinogenicity with an overexpression model. In the present study, a CRISPR/dCas9 system was applied to construct the CENPF overexpression model. CENPF was upregulated and downregulated to analyze its functions in vitro. CENPF knockdown cell models showed inhibition of HCC proliferation. Notably, as a cell cycle protein with high constitutive expression in G2/M phase, CENPF overexpression cell models also showed inhibitory effects, probably due to the toxic effect of excessive CENPF expression on G2/M transition. However, in both CENPF downregulation and overexpression models, cell cycle assays showed CENPF promoted G1/S transition in HCC cells. RNA-seq showed that CENPF overexpression activated the MYC pathway, thereby promoting G1/S transition. The rescue experiment indicated that the MYC pathway inhibitor 10058-F4 counteracted the G1/S transition induced by CENPF overexpression in HCCLM3 cells. CENPF overexpression might facilitate HCC cells G1/S cell cycle transition via the MYC pathway.
2026-04-15 | GSE319803 | GEO
Project description:Background: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. Objectives: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. Methods: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. Results: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surfaceM-bM-^@M-^Sassociated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. Conclusions: UNC50 is a potential oncogene that promotes HCC progression by affecting the EGFR pathway. To gain insight into the role UNC50 plays in HCC progression, we used microarray analyses to identify indirect evidence of UNC50 gene function via the knockdown strategy in Hep3B cells. Hep3B cells transfected with the shRNA expression plasmids shR-467, shR-554, shR-749, and shR-MOCK were purified with 1ug/ml puromycin, and the total RNA from each cell was extracted and analyzed with oligo microarrays.
2014-11-17 | E-GEOD-63322 | biostudies-arrayexpress
Project description:Background: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. Objectives: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. Methods: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. Results: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surface–associated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. Conclusions: UNC50 is a potential oncogene that promotes HCC progression by affecting the EGFR pathway.
2014-11-17 | GSE63322 | GEO
Project description:Transforming growth factor-β (TGF-β) signaling and cellular senescence are key hallmarks of hepatocellular carcinoma (HCC) pathogenesis. While provoking senescence-associated growth arrest in epithelial HCC cells, elevated TGF-β activity paradoxically correlates with aggressiveness and poor prognosis in advanced tumors. Whether the transition between these dichotomous functions involves bypassing the senescence barrier during disease progression remains unknown. Exploiting the epithelial HCC cell line Huh7, we demonstrate that chronic TGF-β exposure prompts escape from Smad3-mediated senescence, leading to the development of TGF-β resistance. The resistant state is characterized by restoration of proliferative capacity and acquisition of molecular and functional traits of mesenchymal cells, coinciding with hybrid EMT, increased invasiveness, and metastasis. Mechanistically, resistant cells exhibit defective signaling of Smad molecules, as ectopic activation of the TGF-β/Smad3 axis reinstates TGF-β sensitivity. Gene expression landscape profiling reveals both shared and distinct gene signatures associated with senescent and TGF-β resistant states. Importantly, genetic ablation and molecular studies identify GRM8 (Glutamate Metabotropic Receptor 8) as a critical modulator of the resistance phenomenon, potentially by impairing subcellular spatiotemporal dynamics of Smad activity. Our findings unveil a novel phenomenon wherein epithelial HCC cells may exploit senescence evasion as a mechanism to oppose TGF-β anti-tumor responses and progress towards more aggressive HCC phenotypes.
2025-03-17 | GSE261099 | GEO
Project description:Hepatocellular Carcinoma (HCC) is a disease with an increasing incidence and a high mortality rate; therefore, targeted therapies for HCC are urgently needed. PI3K-AKT-mTORC1 signaling is frequently induced in solid tumors and is associated with tumor progression and with the most aggressive type of HCC. However, complete inhibition of all PI3K isoforms is unlikely to achieve a favorable therapeutic index for HCC treatment due to on-target side effects. Here, we investigate the role of hepatocyte PI3Ka in HCC using conditional knockout mice. We found that PI3Ka in the hepatocyte is dispensable for AKT phosphorylation in HCC and in normal liver, and hepatocytes during compensatory proliferation following administration of the hepatocarcinogen. We have also found that AKT phosphorylation induced by hepatocyte growth factor (HGF) and epidermal growth factor (EGF) is mediated by redundant PI3Ka and PI3Kb activities. Nonetheless, mice lacking hepatocyte PI3Ka showed reduced HCC proliferation and reduced hepatocyte proliferation induced by DEN. This phenotype was associated with a gene expression signature indicating altered lipid metabolism and reduced formation of lipid droplets. Together, these results indicate that PI3Ka is a promising target for the treatment of HCC.
2026-04-30 | GSE302836 | GEO
Project description:Using a kinome-centred CRISPR/Cas9 genetic screen, we identify here that inhibition of the epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer cells. We found that the combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effect in HCC cell lines that express EGFR in vitro and of xenografted HCC cell lines or patient-derived HCC tumours in mice. Herre, we analyzed the different transcriptome profiling of HCC cells treated with DMSO, lenvatinib, gefitinib, and lenvatinib plus gefitinib by RNA-sequencing.
2021-07-22 | GSE157905 | GEO
Project description:Cholangiocyte Ciliary Defects Induce Sustained Epidermal Growth Factor Receptor Signaling
| PRJNA1157847 | ENA