Inhibiting TGFβ-1 pathway reduces the aggressiveness of intrahepatic CCA HuCCT1 CD90 positive cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1248463 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33050987.fastq.gz | Fastqsanger.gz | |||
| SRR33050988.fastq.gz | Fastqsanger.gz | |||
| SRR33050989.fastq.gz | Fastqsanger.gz | |||
| SRR33050991.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Molecular mechanisms responsible for the poor prognosis in patients with intrahepatic cholangiocarcinoma (CCA) are still unknown, however, the stem cell marker cluster differentiation 90 (CD90), has been reported to be associated with a more aggressive cancer phenotype. In this scenario, TGFβ1 signaling pathway likely has a role as master gene regulator. Aim of the study is to investigate the role of CD90 in iCCA aggressiveness. The molecular profile of HuCCT1/CD90+ and HuCCT1/CD90- cells was obtained through transcriptomic analysis (NGS). Bioinformatic data were confirmed in both cell lines by qRT-PCR and western blot. Cells were treated with Gemcitabine in monotherapy or in combination with Galunisertib, a selective TGFβRI inhibitor in 2D and 3D models. HuCCT1 CD90 positive cells are more proliferative, less migratory, and resistant to Gemcitabine treatment. Next, HuCCT1/CD90+ express lower levels of TGFβ1 compared to /CD90- cell lines. Finally, HuCCT1/CD90+ are resistant to Gemcitabine, while the combination of both Gemcitabine and Galunisertib displays a synergistic effect on HuCCT1/CD90+ cell proliferation. These results underline that CD90 inducing Gemcitabine resistance can be overcome by adding a TGFβ1 inhibitor such as Galunisertib, thereby moving further toward a precision medicine approach in patients with iCCA.
2025-06-18 | GSE294148 | GEO
Project description:We examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. Two intrahepatic CCA cell lines, HuH28 and HuCCT1 were used. HuCCT1 cells were more sensitive to Gem than were HuH28 cells. The miRNA expression profiles of HuH28 and HuCCT1 were determined by microarray analysis. Eighteen miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221) restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment.
2013-06-02 | GSE47396 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) is a lethal cancer arising from intrahepatic bile ducts in the liver. In the intraductal growth (IDG) type, also referred to as intraductal papillary neoplasm of the bile duct (IPNB), a rare subtype of ICC, cancer cells originating within the bile duct usually invade and infiltrate the nearby liver tissues, resulting in local invasion. IPNB can serve as a good disease model to study the mechanism of local invasion, which is the earliest step of metastasis. Here, we aimed to identify the genes associated with local invasion by comparing the somatic mutations of the matched IPNB tissues with and without local invasion from a set of 11 patients using the Ion AmpliSeq Comprehensive Cancer Panel. Somatic mutation profiling analysis identified RNF213 as a potential candidate gene associated with local invasion in ICC patients. We established stable RNF213-knockdown and shControl cholangiocarcinoma (CCA) cell lines (HuCCT1, YSCCC, and KKU-100). Next, the expression profiling of the RNF213-knockdown and shContol CCA cell lines was analyzed by RNA sequencing.
2024-07-24 | GSE235891 | GEO
Project description:We examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. Two intrahepatic CCA cell lines, HuH28 and HuCCT1 were used. HuCCT1 cells were more sensitive to Gem than were HuH28 cells. The miRNA expression profiles of HuH28 and HuCCT1 were determined by microarray analysis. Eighteen miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221) restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Cell lines and cultures Two human intrahepatic CCA cell lines, HuCCT1 and HuH28, were purchased from Japan Health Science Research Resources Bank (Osaka, Japan). Each cell line was cultured in RPMI-1640 medium (Invitrogen, Life Technologies Corp., CA, USA) that contained 10% fetal bovine serum (Nichirei Bioscience, Tokyo, Japan) and in humidified conditions at 37 ˚C and 5% CO2. Antibiotics were not added to the culture medium when cells were prepared for transfection with miRNA mimics or oligonucleotides. Gem treatment Gem hydrochloride was purchased from Wako (Osaka, Japan). A stock solution was prepared at 1 mmol/L (1 x 10-3 M) and was further diluted to anyone of several different final working concentrations from 1 x 10-4 to 1 x 10-7 M with cell culture medium that lacked antibiotics. Transfection of miRNA mimics, antisense oligonucleotides, or siRNA for miRNA target genes were performed 24 hr before the Gem treatment. All assays were conducted 72 hr after Gem treatment.
2013-06-02 | E-GEOD-47396 | biostudies-arrayexpress
Project description:RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma
| PRJNA488800 | ENA
Project description:Intrahepatic cholangiocarcioma has two molecular classification of intrahepatic CCA with distinct clinical, pathological, biological and prognostic differences
2018-12-01 | GSE107943 | GEO
Project description:Glycosphingolipids (GSL), a class of plasma membrane lipids, have been proposed as markers of cancer stem cells (CSC). In particular, gangliosides (GS), sialic acid-containing GSL, have been investigated for their role in the malignant phenotype of several cancers and in tumor-stem like cells, but there are no data about human cholangiocarcinoma (CCA). Our study aims to provide a GSL and GS profiling of both stem-like subsets and their parental cells in human CCA. Experimentals. Intrahepatic CCA cells (HUCCT1, CCLP1) were used. Stem-like subset was enriched by sphere culture (SPH) and compared to parental cells grown as monolayer (MON). CCA GS patterns were determined by chromatographic analytical procedures, and their molecular species identification was evaluated by feeding cells with 3H-sphingosine. GS role in modulation of stem features was investigated using D- threo-1phenyl-2-palmitoylamino-3-N-morpholine-1-propanol (PPMP, glucosylceramide synthase inhibitor), and CCA GD3S-transfected cells. FACS-sorted GD2+ SPH cells were examined for stem-like gene expression compared to GD2- SPH. GS biosynthesis enzymes were analyzed by RT-qPCR at different times of spherogenesis. Results: In both CCA lines, compared to MON, SPH showed drastic changes in specific sphingolipids (Cer, Gb3, SM), and in the amount of total GS. In contrast to MON, CCA-SPH shows increase content of GM3, reduction of GM2; among complex GS, strongly increase of GD1a and appearance of GD2, a finding also corroborated by high levels of GM3 synthase as well as GD3- and GM2/GD2 synthases expression in CCA-SPH. Notably, sphere-forming ability and expression of CSC-related genes were affected by PPMP. Importantly it has emerged that the cancer stem features related on GD2 availability are not due to the ganglioside GD2 synthase enzyme, but depend on the enzyme GD3S, the synthase that provides the precursor (GD3) of ganglioside GD2. Thus we have stably transfected both CCLP1 and HUCCT1 cells with the GD3S gene. GD3S-transfected MON (MON GD3S+) cells showed enhanced sphere-forming ability in vitro, superior invasive properties, as well as higher drug resistance when treated with cisplatin and oxaliplatin compare to the transfected control. To better clarify the molecular features and the altered pathways in MON GD3S+ CCA cells, a global transcriptomic analysis was performed. Likewise, GD2+ SPH cells were enriched with CSC-markers at protein and gene levels in addition to several genes involved in pluripotency, self-renewal, and EMT, compare to GD2- SPH. Notably, expression of GM2/GD2 synthases was significantly expressed in tumor samples compared to paired non-tumoral liver tissue of CCA patients (n=104) and greatly correlated with presence of satellite nodules, lymph node invasion, and recurrence. Conclusions: We show for the first time that the CCA stem-like properties may be associated with GSL synthetic pathway and pattern. GSL and GS synthases could represent potential markers for CCA.
2025-01-08 | GSE238179 | GEO
Project description:RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [SNP]
| PRJNA488804 | ENA
Project description:Intrahepatic Cholangiocarcinoma (iCCA) is a difficult type of cancer to diagnose, extremely aggressive and resistant to therapeutic options with an increased incidence and mortality over time. The overexpression of Notch pathway is implicated in iCCA to create an ecosystem that drives the tumor aggressiveness. Specifically, Notch1 is overexpressed in iCCA tissue of patients, playing an important role on tumor growth. Our purpose was to investigate the effectiveness of Crenigacestat in in vivo experiments, using Hucct1 injected in CD1 mice to generate an iCCA xenograft mouse model. In the present study, in order to explore modulated factors and genes by treatment we performed a transcriptomic analysis validated by Western Blotting and qRT-PCR on iCCA tumor masses of xenograft mice. Our results indicate that the treatment significantly inhibited Notch1 and HES1 genes and proteins triggering a strong immune response. Nevertheless, moderate fibrosis was shown in this model which may have hindered response to therapy to promote tumor progression. We used microarray technology to understand the molecular mechanisms affected by Crenigacestat in HUCCT1 xenograft model of intraepatic cholangiocarcinoma.
2022-04-27 | GSE150024 | GEO
Project description:RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [RNA-Seq]
| PRJNA488803 | ENA