MiRNA expression profiling in cholangiocarcinoma (CCA) cells compared to non-malignant human cholangiocyte
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PROVIDER: PRJNA497522 | ENA |
REPOSITORIES: ENA
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Project description:Expression profiling of 2555 miRNAs was performed using microarray. Of these, 508 miRNAs expressed in both of CCA and non-malignant human cholangiocyte.
2019-10-19 | GSE121512 | GEO
Project description:Background and aims: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. Incidence is increasing worldwide and these cancers collectively represent the second most common primary liver tumour. CCAs are characterized by genetic and epigenetic alterations that determine their pathogenesis. Hypermethylation of the SOX17 promoter was recently reported in human CCA tumours. SOX17 seems to be a key transcription factor for biliary embryogenesis. Here, we evaluated the role of SOX17 in cholangiocyte differentiation and in cholangiocarcinogenesis. Methods: SOX17 expression and function was evaluated during the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation of normal human cholangiocytes (NHC) and in cholangiocarcinogenesis. Lentiviruses overexpressing or knocking-down SOX17 (Lent-SOX17 and Lent-shRNA-SOX17, respectively) were used. Gene expression arrays were performed. Results: SOX17 expression is highly induced in the later stages of cholangiocyte differentiation from iPSC, and mediates the acquisition of the biliary markers cytokeratin (CK) 7 and 19, as well as fibronectin. In addition, SOX17 becomes progressively downregulated in NHC over serial cell passages in vitro and this event is associated with cellular senescence; however, experimental SOX17 knocking-down in differentiated NHC decreased the expression of both CK7 and 19 without affecting cellular senescence. SOX17 expression is reduced in CCA cells compared to NHC, as well as in human CCA tissue compared to human gallbladder tissue or NHC. In a murine xenograft model, overexpression of SOX17 in CCA cells decreased their tumorigenic capacity related to increased oxidative stress and apoptosis. Interestingly, overexpression of SOX17 in NHC did not affect their survival. Moreover, SOX17 overexpression inhibited the Wnt/β-catenin-dependent proliferation in CCA cells and was associated with upregulation of biliary epithelial markers and restoration of the primary cilium length. Both Wnt3a and TGFβ1 decreased SOX17 expression in NHC in a DNMT1-dependent manner. Inhibition of DNMT1 in CCA cells with siRNAs or pharmacological drugs upregulated SOX17 expression. Conclusion: SOX17 regulates the cholangiocyte phenotype and becomes epigenetically downregulated in CCA. SOX17 acts as a tumour suppressor in CCA, and restoration of its expression may have important therapeutic value.
2017-08-31 | GSE77984 | GEO
Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.
2022-05-04 | GSE179597 | GEO
Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.
2022-05-04 | GSE179599 | GEO
Project description:Cholangiocarcinoma (CCA) is a type of highly aggressive cancer arising from the biliary system. Through serum exosome miRNA sequencing, we screened out the differentially expressed miRNA in patients with cholangiocarcinoma(CCA) and common bile duct stones(CBDS).
2022-10-20 | GSE215448 | GEO
Project description:Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis. We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. Our findings show that lncRNAs may be potential biomarkers of CCA progression.
2017-09-16 | GSE103909 | GEO
Project description:RNA sequencing profiles of immortalized cholangiocyte and cholangiocarcinoma cell lines in untreated (basal), dasatinib-treated, and PD-0325901-treated states.
2022-09-30 | GSE125035 | GEO
Project description:Cholangiocarcinoma (CCA) represents a heterogeneous group of biliary cancers with poor prognosis. Although the aetiology is generally unknown, factors like Primary Sclerosing Cholangitis (PSC) predispose to its development. Simultaneously, around 80% of patients with PSC have concomitant Ulcerative Colitis (UC). As there are no specific and sensitive biomarkers for the non-invasive diagnosis of CCA, we aimed to analyse the RNA content of serum and urine extracellular vesicles (EVs) to find accurate biomarkers of CCA that could be reflecting tumor behaviour. The transcriptomic analysis of these EVs showed a differential profile of RNAs in patients with CCA compared to healthy individuals or patients with other diseases (PSC and UC), presenting some RNAs high diagnostic values to distinguish patients with CCA. Moreover, the differential abundance of several RNAs in serum and/or urine EVs correlated with the deregulated expression of those transcripts in CCA tissue compared to surrounding liver (TCGA and Copenhagen cohorts), in tumor (EGI1, TFK1) and normal cholangiocyte (NHC) cell lines as well as in EVs secreted by those cell lines; pinpointing the potential involvement of those RNAs not only as liquid biopsy biomarkers but also as potential mediators of CCA pathogenesis.
2020-05-18 | GSE144521 | GEO
Project description:A cholangiocarcinoma cell line was used to inhibit FOSL1 and study dowsntream effectors in vitro
2023-07-22 | GSE154954 | GEO
Project description:We report the characterization of FOSL1-bound transcriptional targets in CCA cells. Target genes include different RNA species involving protein coding genes, lncRNA, miRNA and others
2023-07-22 | GSE154953 | GEO