Investigation of mechanism using highly intrahepatic metastatic cell lines of HCC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151169 | GEO | 2021/03/23
REPOSITORIES: GEO
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Project description:Investigation of mechanism using highly intrahepatic metastatic cell lines of HCC
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Project description:Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher the role of EV cargo in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of extracellular vesicles (EVs) derived from human primary tumor (SCC-9) cells and matched lymph node metastases (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 64 lipids differentially abundant between LN1- and SCC-9-derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared to primary tumor-derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases, and found that low abundance of seven hub proteins in metastatic EVs is correlated with reduced survival and tumor aggressiveness in cancer patients. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis, and which may potentially serve as prognostic markers in OSCC.
2021-04-26 | ST001755 | MetabolomicsWorkbench
Project description:Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features. Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes. Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.
2022-07-12 | GSE179443 | GEO
Project description:Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma
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Project description:Using the highly sensitive cricRNA array, we screened functional circRNAs in the human highly/low invasive HCC tissues, and the function of differentially expressed circRANs were analyzed by bioinformatics. The results revealed that circASH2 inhibits HCC metastasis by circASH2/YBX1/hnRNPs/TPM4 axis.
2023-07-02 | GSE235991 | GEO
Project description:BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (As2O3, ATO, arsenious acid), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including liver cancer. Although the mechanistic effects of ATO in APL are established, its anticancer mechanism of action in HCC is still unclear. METHODS: We established an HCC subcutaneous xenograft and intrahepatic metastasis mouse model. In CSC models, tumorspheres and the flow cytometry analysis of CSC markers together with limiting dilution and serial transplantation were used. We compared mRNA expression profiles of the ATO-treated and control cells with mRNA microarray. The expression of target molecule or a clinical correlation was analyzed by immunohistochemistry staining in tissues from ATO-treated mouse and 76 HCC patients. We generated five stable minichromosome maintenance protein 7 (MCM7)-knockdown and two stable MCM7-overexpression HCC cell lines. The chromatin immunoprecipitation (ChIP) assays, immunoprecipitation (IP) assays, the dual luciferase reporter assays, a green biarsenical labeling reagent (FlAsH-EDT2) and a “competing endogenous RNA” (ceRNA) analysis were used. RESULTS: ATO could inhibit the liver tumor-initiating capacity and distant metastasis and prolongs survival in mice. We then screened and found that ATO downregulates the overexpression of MCM7 which is correlated with the progression and prognosis in HCC patients. Knockdown of MCM7 expression recapitulates the inhibition function of ATO on self-renewal of cancer stem cells (CSCs), while overexpression of MCM7 abolishes the inhibition function of ATO on tumorsphere formation. Most importantly, we revealed that ATO directly binds to the MCM7 protein and disturbs the interaction between serum response factor (SRF) and MCM7, resulting in downregulation of MCM7 transcription. A ceRNA analysis also indicated the alterations of endogenous MCM7-associated gene networks involved in stemness-related signaling pathways and cell differentiation. CONCLUSIONS: Here, for the first time, we report that ATO inhibits liver CSCs through blocking the interaction between SRF/MCM7 and suppressing MCM7 autoregulation activity.
2019-07-02 | GSE111935 | GEO
Project description:Comparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression. Mice were orthotoplically transplanted with MDA-MB-231 Breast Adenocarcinoma cells. Cells and extracellular vesicles (EVs) from the resulting tumors were isolated. EVs were characterized by electron microscopy and Nanoparticle Tracking Analysis before total RNA isolation for comparative analysis with cellular RNA. Three biological replicates were analyzed in (technical) duplicate.
2015-03-05 | E-GEOD-66488 | biostudies-arrayexpress
Project description:Extracellular vesicles (EVs) play a crucial role in facilitating intercellular communication. The microRNA profiles carried by EVs often exhibit variations between tumor patients and healthy individuals, making them promising biomarkers. These biomarkers are implicated in oncogenic processes and tumor metastasis upon uptake by recipient cells. To investigate the impact of EV biomarkers on tumorigenesis, we exposed HCT-116 cell lines to EVs isolated from the serum of both tumor patients and healthy individuals. In comparison to cell lines treated with extracellular vesicles (EVs) from healthy individuals and blank controls, cell lines treated with EVs from HCC sources exhibit significant alterations in the expression of certain genes associated with pathways related to liver cancer. Our findings shedlight on the intricate interplay between EVs and tumor progression.
2024-05-12 | GSE266634 | GEO
Project description:Metastasis, especially intrahepatical, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously we reported HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as important regulators of various cellular processes and has been implicated in the cancer progression. Here we uncovered a novel nuclear circRNA, circASH2, which is preferentially lost in HCC tissues, and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was post-transcriptionally suppressed. Such regulation is based on mRNA/pre-mRNA splicing and degradation process. Furthermore, liquid-liquid phase separation (LLPS) of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a novel tumor suppressive circRNA and more importantly, uncovered a fine regulation mechanism for HCC progression.
2023-07-02 | GSE236039 | GEO
Project description:Cancer-associated fibroblasts (CAFs) have an important role in the tumor progression. CAFs are heterogeneous, and its subpopulation with distinct functions have been regarded as the major obstacle to CAF targeting therapy. However, it is still unclear how cancer cells mediate CAF subpopulations and create preferable tumor microenvironment for their metastasis. In this study, by using the metastatic cancer cell line models of diffuse-type gastric cancer (DGC), we demonstrate that high-metastatic cancer cell-derived extracellular vesicles (EVs) contribute to the formation of activated fibroblast subpopulations. High-metastatic DGC cells create at least two types of CAF subpopulations: myofibroblastic feature and chemokine producing feature. The CAF subpopulation with chemokine producing feature was selectively induced by high-metastatic DGC cell-derived EVs. We also found that high-metastatic DGC cell-derived EVs contain various miRNAs to induce chemokine expression in the fibroblasts. Our findings suggest that intercellular communications via EVs contribute to establishing the appropriate tumor microenvironment toward cancer metastasis. To study the effect of EVs derived from GC cell lines on gene expression in the stomach fibroblasts, transcriptome analysis for the stomach fibroblasts with EVs derived from GC cell lines was performed.
2019-03-31 | GSE116176 | GEO