CircZKSCAN1 suppresses stemness in hepatocellular carcinoma (HCC) by competing against RNA-binding protein FMRP
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA432661 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6666070_1.fastq.gz | Fastqsanger.gz | |||
| SRR6666070_2.fastq.gz | Fastqsanger.gz | |||
| SRR6666071_1.fastq.gz | Fastqsanger.gz | |||
| SRR6666071_2.fastq.gz | Fastqsanger.gz | |||
| SRR6666072_1.fastq.gz | Fastqsanger.gz |
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Project description:Background & Aims CTNNB1-mutated HCCs exhibit a relatively low stem-like and well-differentiated phenotype. However, the mechanism remains unclear. Ripply transcriptional repressor 1 (RIPPLY1), a transcriptional repressor required for somite segmentation, has hardly been studied in cancer. Here, we aim to unveil the role of RIPPLY1 in the regulation of cancer cell stemness in CTNNB1-mutated HCCs. Approach and Results RIPPLY1 was found to be transactivated by the Wnt/β-Catenin signal pathway. Human sample analysis confirmed that RIPPLY1 was significantly upregulated in CTNNB1-mutated HCC tissues and positively correlated with better prognosis of HCC patients. Hepatocyte-specific deletion of RIPPLY1 promoted tumorigenesis and progression in DEN/PB-induced CTNNB1-mutated HCC mouse model and hydrodynamic tail-vein injection (HDTVi)-induced CTNNB1-mutated HCC mouse model. RIPPLY1 knockout tumor cells displayed upregulated levels of stem cell makers and enhanced cancer stem cell properties. Co-IP and MS identified TBX19 as the target protein of RIPPLY1. RIPPLY1 suppressed the transcriptional activity of TBX19 via recruiting TLE1 and promoting proteasome-dependent degradation of TBX19. TBX19 deficiency abolished the effect of RIPPLY1 loss on cancer cell stemness in CTNNB1-mutated HCCs. Conclusion： Loss of RIPPLY1 promotes cancer cell stemness via facilitating the TBX19 transcriptional activity in CTNNB1-mutated HCCs.
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Project description:To investigate the role of ADAR1in HCC development and stemness maintenance, we established HCC cell lines in which ADAR1 has been knocked down by shRNA or overexpressed. We then performed gene expression profiling analysis using data obtained from RNA-seq of 8 different cells
2022-07-23 | GSE208358 | GEO
Project description:Background & Aims: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells and their local and distant microenvironment. Here, we aimed to understand the role and molecular basis of patient-derived EVs in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). Methods: EVs were isolated, quantified and characterized from patients’ sera. EVs were tested vigorously, both in vitro and in vivo, by various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The expression level of polymeric immunoglobulin receptor (pIgR) in circulating EVs, tumor and non-tumorous tissues of HCC patients was determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with an enhanced pIgR expression was elucidated. Blockage of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenograft (PDTX). Results: Circulating EVs of late-stage HCC (L-HCC) patient had significantly elevated pIgR expression when compared to the EVs released by control individuals. The augmenting effect of L-HCC patient in cancer stemness and tumorigenesis was hindered by anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in the recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and β-catenin inhibitors, ascertaining the role of EV-pIgR through the activation of PDK1/Akt/GSK3β/β-catenin signaling axis. Furthermore, anti-pIgR neutralizing antibody attenuated the tumor growth in mice implanted with PDTX. Conclusion: The study illustrates an unrevealed role of EV-pIgR in regulating cancer stemness and aggressiveness, in which EV-pIgR activates PDK1/Akt/GSK3β/β-catenin signaling cascades. The blockage of intercellular communications mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for cancer patients.
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2013-10-25 | E-GEOD-41874 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples and found that YTHDF1 was significantly upregulated in HCCs with high stemness scores and was positively associated with recurrence and poor prognosis. Analysis of hepatoma spheroids revealed that YTHDF1 was highly expressed in liver cancer stem cells (CSCs). Stem cell-specific conditional Ythdf1 knock-in (CKI) mice treated with diethylnitrosamine showed elevated tumor burden compared with wild type mice. YTHDF1 promoted CSC renewal and resistance to the multiple tyrosine kinase inhibitors lenvatinib and sorafenib in patient-derived organoids and HCC cell lines, which could be abolished by catalytically inactive mutant YTHDF1. RNA immunoprecipitation sequencing, m6A methylated RNA immunoprecipitation sequencing, ribosome profiling, and RNA sequencing identified NOTCH1 as a direct downstream of YTHDF1. YTHDF1 bound to m6A modified NOTCH1 mRNA to enhance its stability and translation, which led to increased NOTCH1 target genes expression. NOTCH1 overexpression rescued HCC stemness in YTHDF1 deficient cells in vitro and in vivo. Lipid nanoparticles targeting YTHDF1 significantly enhanced the efficacy of lenvatinib and sorafenib in HCC in vivo. Taken together, YTHDF1 drives HCC stemness and drug resistance through a YTHDF1-m6A-NOTCH1 epitranscriptomic axis, and YTHDF1 is a potential therapeutic target for treating HCC.
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Project description:c-Met induces tumor initiation and stemness in HCC cells through the regulation of CD44s via AKT signaling. Over-expression of CD44s in c-Met and CD44s negative cells induce both a stemness and mesenchymal phenotype independent of c-Met. The down regulation of CD44s or c-Met was compared to Scrambled control to investigate the effects of CD44s or c-Met on global changes of mesenchymal or stemness markers.
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Project description:Background:
There are about 100 trillion microbial cells in a person s gut. This is called the human gut microbiota. When this is disrupted, it can lead to many diseases. Studies show that the gut microbiota in people with cancer is different than that found in healthy people. Researchers want to study links between the gut microbiota and the immune system in people with a liver disease called hepatocellular carcinoma (HCC).
Objective:
To study links between gut microbiota and the immune system in people with HCC.
Eligibility:
People at least 18 years old with HCC. They must be scheduled to have tumors removed by surgery.
Design:
* People having surgery for primary liver tumors at the Mount Sinai Medical Center will be screened for this study.
* At the initial visit, blood, rectal swabs, urine, and stool will be collected. Participants will answer questions about their medical condition.
* Before surgery, blood, rectal swabs, urine, and stool will be collected. This will be done at a routine visit.
* When they have surgery, a piece of liver tissue with the tumor will be collected. This will be sent to the National Cancer Institute for tests.
* After surgery, blood, rectal swabs, urine, and stool will be collected 3 times. This will be done at routine visits.
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Project description:DNA copy number profiling for all primary tumor samples and HCC cell lines was performed by ROMA, a form of comparative genomic hybridization. The aim was to identify commonly amplifiied and deleted regions across human HCC. 88 primary HCC samples and 12 human HCC cell lines were analyzed.
2011-01-10 | E-GEOD-22916 | biostudies-arrayexpress