XBP1s cooperates with LEF1 to promote hepatocellular carcinoma development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164615 | GEO | 2021/01/12
REPOSITORIES: GEO
Similar Datasets
Project description:In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. By RNA-seq, ATAC-seq and CUT&Tag-seq analysis, we found that long-term MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, which was causal to the activation of the IRE1α-XBP1s axis of the unfolded protein response. Furthermore, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells.
2023-11-30 | GSE248562 | GEO
Project description:The proteomic profiling of nine commonly used HCC cell lines Hep3B, HepG2, HepG2.2.15, HUH7, PLC/PRF/5, MHCC97L,MHCC97H,HCCLM3 and HCCLM6
2022-11-11 | PXD036643 | Pride
Project description:Purpose: We performed RNA sequencing (RNA-seq) analysis to investigate the role of ZCCHC4 in regulating OXA-induced genes in HepG2 cells. The goal of this study is to investigate the biological effect of ZCCHC4 in HCC progression and prognosis, and we have found that ZCCHC4 could promote chmoresistance of HCC to DNA damage agents including OXA, we conducted RNA-seq to figure out more clues for deep mechanisms.
2022-07-27 | GSE190632 | GEO
Project description:The unfolded protein response (UPR) has emerged as important signaling pathway mediating anti-viral defenses to Respiratory Syncytial Virus (RSV) infection. In this study, we examine how Inositol Requiring Enzyme (IREa X-Box Binding Protein spliced (XBP1s) arm of the Unfolded Protein Response (UPR) pathway controls the innate response integrating RNA-seq and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) analyses. XBP1s binds to ~4.2 K high-confidence genomic binding sites. Surprisingly these map to only a small subset of IL10/cytokine genes. We further find that that RSV infection enhances XBP1s occupancy on 786 genomic sites enriched in AP1/Fra-1, RELA and SP1 binding sites controlling a core subset of cytokine regulatory factors genes including IFN response factor 1 (IRF1), CSF2, NFKB1A and DUSP10. Selective IRF1 knockdown experiments demonstrates its requirement in control of type I and -III IFNs and IFN-stimulated genes (ISGs) indicating these genes are indirectly regulated through IRF1 transactivation. We conclude that RSV modulates the XBP1 binding complex to the IRF1 epromoter, providing novel insight into how the IRE1-XBP1s pathway potentiates airway mucosal anti-viral responses.
2023-04-30 | GSE228328 | GEO
Project description:Hepatocellular carcinoma (HCC) ranks sixth among the most common malignancies and fourth in mortality among all kinds of cancers in the world. Recent advances in early diagnosis and therapeutics have led to improved survival of HCC patients, but the recurrence and metastasis are still main reasons for the poor prognosis and high mortality of HCC. Many researches on the mechanism of HCC deterioration have uncovered the epithelial-mesenchymal transition (EMT) as a major trigger for HCC metastasis and invasion.In this study, in order to systematically investigate the dynamic site-specific glycosylation alterations associated with the EMT process of HCC, two hepatoma cell lines SMMC-7721 and HepG2 were treated using HGF and the cell proteins were harvested at six treatment time points. Using TMT-labeling, solid phase extraction and mass spectrometry, we not only detailly profiled N-glycoproteome of both cell lines at site-specific glycosylation level, but also dynamically quantified those intact glycopeptides among six increasing HGF-treated time points. By dynamically quantifying enriched glycopeptides and proteins among six HGF-treated time points in two cell lines, we identified 20 up-regulated intact glycopeptides during the process of EMT, with the majority changed at the glycosylation level instead of protein expression level. The site-specific glycosylation change of those glycoproteins was related to the process of EMT, which was further verified by a series of molecular biology methods, mass spectrometry, and migration and invasion assay in vitro.
2021-09-09 | PXD017033 | Pride
Project description:Analysis of Xbp1s overexpression in liver after 24 hr indution or 48 hr induction in LIXs mouse. As a control, WT mice after 2 hr refeed and 24 hr fast without refeed are used for analysis of postprandial gene expression. This microarray study was used to screen for target genes activated by Xbp1s in liver. Results provide important information for the role of Xbp1s during postprandial. Total RNA obtained from liver tissues from mice on Dox200 chow diet for 24 hr or 48 hr. Mice were fasted for 6 hr before sacrifice for liver.
2013-01-08 | E-GEOD-39301 | biostudies-arrayexpress
Project description:Emerging evidences indicate that microRNAs (miRNAs) are often deregulated and have fundamental roles in hepatocellular carcinoma (HCC). However, the mechanism underlying miRNA dysregulation in HCC is still elusive. In this report, we used an integrated analysis strategy combining methylated DNA immunoprecipitation chip (MeDIP-chip) and miRNA expression microarray data to study the correlation between aberrant methylation and dysregulation of miRNA in HCC. In all, we showed that global miRNA methylation profiles were significantly different between cancerous and normal hepatocytes, and abnormal methylation was an important mechanism governing miRNA expression in HCC. MeDIP-chip was processed in cancerous hepatocytes SK-HEP-1, HepG2, MHCC97-H and normal hepatocytes PHHC-4-1, PHHC-4-2, PHHC-4-3 (3 technical repeat of PHHC-4). MiRNA microarray were processed for cancerous hepatocytes SK-HEP-1, HepG2, Hep3B, Huh7, MHCC97-H, MHCC97-L, SMMC-7721 and normal hepatocytes PHHC-1, PHHC-2, PHHC-3. Then an integrated analysis strategy combining MeDIP-chip and miRNA expression microarray [GSE20077] were used to study the correlation of aberrant DNA methylation and dysregulation of miRNAs.
2015-08-05 | E-GEOD-49554 | biostudies-arrayexpress
Project description:The molecular mechanisms of carcinogenesis have been deeply studied benefit from the highly developing biotechnologies. Here we used high throughput sequencing method to capture the global binding profiles on RNA and DNA of EZH2 and JARID2 in liver normal (THLE-2) and carcinoma (HepG2) cells, respectively. We found that EZH2 and JARID2 showed distinct binding profile in HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional level in hepatocellular carcinoma (HCC) patients. They bound transcripts were also highly related to the HCC development by performing gene set enrichment analysis (GSEA). By exploring the DNA binding profile, we also detected similar phenomena that EZH2 could increase the transcriptional level of bound genes in HepG2 cells, showing PRC2-independent functions in liver cancer cells. Integrating analysis of the RNA and DNA binding profile showed EZH2 could independent function at the transcriptional and post-transcriptional stages. In summary, we proposed that the novel regulatory functions of EZH2 and JARID2 that may promote the cancer development in carcinoma liver cells.
2022-07-04 | GSE133982 | GEO
Project description:The molecular mechanisms of carcinogenesis have been deeply studied benefit from the highly developing biotechnologies. Here we used high throughput sequencing method to capture the global binding profiles on RNA and DNA of EZH2 and JARID2 in liver normal (THLE-2) and carcinoma (HepG2) cells, respectively. We found that EZH2 and JARID2 showed distinct binding profile in HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional level in hepatocellular carcinoma (HCC) patients. They bound transcripts were also highly related to the HCC development by performing gene set enrichment analysis (GSEA). By exploring the DNA binding profile, we also detected similar phenomena that EZH2 could increase the transcriptional level of bound genes in HepG2 cells, showing PRC2-independent functions in liver cancer cells. Integrating analysis of the RNA and DNA binding profile showed EZH2 could independent function at the transcriptional and post-transcriptional stages. In summary, we proposed that the novel regulatory functions of EZH2 and JARID2 that may promote the cancer development in carcinoma liver cells.
2022-07-04 | GSE133980 | GEO
Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.
2013-11-21 | E-GEOD-36031 | biostudies-arrayexpress