Similar Datasets
Project description:PABPC4 is a member of the poly(A)-binding protein (PABP) family, responsible for regulating post-transcriptional gene expression. While PABPC1 is widely expressed and has a general function in translation initiation and mRNA stability, PABPC4 shows lower expression levels and a more tissue-specific pattern. It plays a role in specific biological processes such as erythroid differentiation and oogenesis. The precise regulation and specific role of PABPC4 in hepatocellular carcinoma (HCC) have remained unclear despite previous studies highlighting its involvement in HCC cell lines. To uncover potential downstream targets of PABPC4 in HCC cells, we conducted RNA-seq and RIP-seq analyses to identify mRNAs that were both downregulated in PABPC4-deficient cells and bound by PABPC4.
2024-06-01 | GSE233709 | GEO
Project description:PABPC4 is a member of the poly(A)-binding protein (PABP) family, responsible for regulating post-transcriptional gene expression. While PABPC1 is widely expressed and has a general function in translation initiation and mRNA stability, PABPC4 shows lower expression levels and a more tissue-specific pattern. It plays a role in specific biological processes such as erythroid differentiation and oogenesis. The precise regulation and specific role of PABPC4 in hepatocellular carcinoma (HCC) have remained unclear despite previous studies highlighting its involvement in HCC cell lines. To uncover potential downstream targets of PABPC4 in HCC cells, we conducted RNA-seq and RIP-seq analyses to identify mRNAs that were both downregulated in PABPC4-deficient cells and bound by PABPC4.
2024-06-01 | GSE233708 | GEO
Project description:Aberrant induction of the rare RNA binding protein PABPC4 in MYC-driven hepatocellular carcinoma
| PRJNA977632 | ENA
Project description:Aberrant induction of the rare RNA binding protein PABPC4 in MYC-driven hepatocellular carcinoma [RNA-seq]
| PRJNA977637 | ENA
Project description:Aberrant induction of the rare RNA binding protein PABPC4 in MYC-driven hepatocellular carcinoma [RIP-seq]
| PRJNA977638 | ENA
Project description:ObjectiveSTK33 has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in hepatocellular carcinoma (HCC) and its underlying mechanisms.Design251 patients with HCC were analysed for association between STK33 expression and clinical stage and survival rate. Tamoxifen (TAM)-inducible, hepatocyte-specific STK33 transgenic and knockout mice models were used to study the role of STK33 in liver tumorigenesis. HCC cell lines were used to study the role of STK33 in cell proliferation in vitro and in vivo.ResultsSTK33 expression was found to be frequently upregulated in patients with HCC. Significant associations were found between increased expression of STK33 and advanced HCC staging and shorter disease-free survival of patients. Overexpression of STK33 increased HCC cell proliferation both in vitro and in vivo, whereas suppression of STK33 inhibited this effect. Using a TAM-inducible, hepatocyte-specific STK33 transgenic mouse model, we found that overexpression of STK33 resulted in increased hepatocyte proliferation, leading to tumour cell burst. Using a TAM-inducible, hepatocyte-specific STK33 knockout mouse model, we found that, when subjected to the diethylnitrosamine (DEN) liver cancer bioassay, STK33KO(flox/flox, Alb-ERT2-Cre) mice exhibited a markedly lower incidence of tumour formation compared with control mice. The underlying mechanism may be that STK33 binds directly to c-Myc and increases its transcriptional activity. In particular, the C-terminus of STK33 blocks STK33/c-Myc association, downregulates HCC cell proliferation, and reduces DEN-induced liver tumour cell number and tumour size.ConclusionsSTK33 plays an essential role in hepatocellular proliferation and liver tumorigenesis. The C-terminus of STK33 could be a potential therapeutic target in the treatment of patients with STK33-overexpressed HCC.
| S-EPMC4717356 | biostudies-literature
Project description:Global transcriptomic imbalance is a ubiquitous feature associated with cancer, including hepatocellular carcinoma (HCC). Analyses of 1,225 clinical HCC samples revealed that a large numbers of RNA binding proteins (RBPs) are dysregulated and that RBP dysregulation is associated with poor prognosis. We further identified that oncogenic activation of a top candidate RBP, negative elongation factor E (NELFE), via somatic copy-number alterations enhanced MYC signaling and promoted HCC progression. Interestingly, NELFE induces a unique tumor transcriptome by selectively regulating MYC-associated genes. Thus, our results revealed NELFE as an oncogenic protein that may contribute to transcriptome imbalance in HCC through the regulation of MYC signaling.
| S-EPMC5539779 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a common cancer that frequently overexpresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical, and molecular changes accompanying HCC progression, regression, and recurrence. These involved altered rates of pyruvate and fatty acid ?-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain complexes I and II to respiration. The uncoupling of complex II's electron transport function from its succinate dehydrogenase activity also suggested a mechanism by which Myc generates reactive oxygen species. RNA sequence studies revealed an orderly progression of transcriptional changes involving pathways pertinent to DNA damage repair, cell cycle progression, insulin-like growth factor signaling, innate immunity, and further metabolic re-programming. Only a subset of functions deregulated in initial tumors was similarly deregulated in recurrent tumors thereby indicating that the latter can "normalize" some behaviors to suit their needs. An interactive and freely available software tool was developed to allow continued analyses of these and other transcriptional profiles. Collectively, these studies define the metabolic, biochemical, and molecular events accompanyingHCCevolution, regression, and recurrence in the absence of any potentially confounding therapies.
| S-EPMC5473214 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options. Genomic amplification and/or overexpression of the MYC oncogene is a common molecular event in HCC, thus making it an attractive target for drug therapy. Unfortunately, currently there are no direct drug therapies against MYC. As an alternative strategy, microRNAs regulated by MYC may be downstream targets for therapeutic blockade. MiR-17 family is a microRNA family transcriptionally regulated by MYC and it is commonly overexpressed in human HCCs. In this study, we performed systemic delivery of a novel lipid nanoparticle (LNP) encapsulating an anti-miR-17 oligonucleotide in a conditional transgenic mouse model of MYC driven HCC. Treatment with anti-miR-17 in vivo, but not with a control anti-miRNA, resulted in significant de-repression of direct targets of miR-17, robust apoptosis, decreased proliferation and led to delayed tumorigenesis in MYC-driven HCCs. Global gene expression profiling revealed engagement of miR-17 target genes and inhibition of key transcriptional programs of MYC, including cell cycle progression and proliferation. Hence, anti-miR-17 is an effective therapy for MYC-driven HCC.
| S-EPMC5814155 | biostudies-literature
Project description:The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.
| S-EPMC10834515 | biostudies-literature