The RNA-Binding Protein DDX39B Promotes Colorectal Adenocarcinoma Progression by Stabilizing DCLK1
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ABSTRACT:
PROVIDER: PRJNA1261940 | ENA |
REPOSITORIES: ENA
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Project description:As an RNA-binding protein (RBP), DDX39B increased the stability of DCLK1-B mRNA, a variant highly expressed in colorectal cancer known to promote cancer stemness, thereby augmenting its protein expression. Notably, silencing of DCLK1-B effectively abrogated the pro-metastatic effects induced by DDX39B overexpression.
2025-06-22 | GSE296923 | GEO
Project description:Doublecortin-like kinase 1 (Dclk1) is known as a cancer stem cell marker of pancreatic ductal adenocarcinoma (PDAC). But the functional evidence to define the stem cell activity of these cells within tumors has not been explored. We compared the gene expression profiles of Dclk1-positive and -negative PDACs cells.
2020-10-20 | GSE139167 | GEO
Project description:Dclk1 (Doublecortin like kinase-1) labels a rare population of long-lived and largely quiescent cells in the adult mouse pancreas. The expression of Dclk1+ vs Dclk1- pancreatic cells (mostly acinar) is observed.
2016-04-11 | GSE74429 | GEO
Project description:Gene expression profiles of Dclk1+ and Dclk1- PDAC cells
| PRJNA578683 | ENA
Project description:Dclk1 expression defines a rare population of cells in normal pancreas whose frequency is increased at early stages pancreatic tumors. The identity and the precise roles of Dclk1 expressing cells in pancreas are matter of debate, although the concept of their involvement in a number of key functions, including regeneration and neoplasia, has emerged. We employed a novel Dclk1 reporter mouse model and single cell RNAseq analysis to define Dclk1 expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas, Dclk1 epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia, Dclk1 expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells represent the main ones. These cells play opposing roles in pancreatic neoplasia, with Dclk1+ ADM-like cells sustaining tumor growth and Dclk1+ tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1+ tuft-like cells requires the activation of SPIB and is further supported by a cellular loop involving cancer group 2 innate lymphoid cells (ILC2) and activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1+ tuft-like cells release angiotensinogen that play protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1+ cells in normal pancreas and also unveils a protective axis against pancreatic neoplasia involving Dclk1+ tuft-like cells, ILC2 and CAFs, which ultimately results in angiotensinogen release.
2024-10-08 | GSE259357 | GEO
Project description:Dclk1 expression defines a rare population of cells in normal pancreas whose frequency is increased at early stages pancreatic tumors. The identity and the precise roles of Dclk1 expressing cells in pancreas are matter of debate, although the concept of their involvement in a number of key functions, including regeneration and neoplasia, has emerged. We employed a novel Dclk1 reporter mouse model and single cell RNAseq analysis to define Dclk1 expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas, Dclk1 epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia, Dclk1 expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells represent the main ones. These cells play opposing roles in pancreatic neoplasia, with Dclk1+ ADM-like cells sustaining tumor growth and Dclk1+ tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1+ tuft-like cells requires the activation of SPIB and is further supported by a cellular loop involving cancer group 2 innate lymphoid cells (ILC2) and activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1+ tuft-like cells release angiotensinogen that play protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1+ cells in normal pancreas and also unveils a protective axis against pancreatic neoplasia involving Dclk1+ tuft-like cells, ILC2 and CAFs, which ultimately results in angiotensinogen release.
2024-10-08 | GSE259356 | GEO
Project description:Dead-box RNA helicases are crucial in mRNA processing, specifically in RNA splicing. Our previous work has shown that DDX39B is responsible for regulating the splicing of IL7R exon 6 and several FOXP3 introns, which rely on DDX39B's helicase and ATPase activities, respectively [this is not accurate since exon 6 also must require the ATPase activity, which is required for helicase activity]. In this study, we aimed to investigate whether DDX39A, a highly homologous paralog of DDX39B, plays a similar role in regulating alternative RNA splicing. We find that DDX39A and DDX39B have significant redundancy in their gene targets, however, DDX39A is incapable of complementing defective splicing of IL7R exon 6 when DDX39B is knockdown. Conversely, overexpressing DDX39A can rescue FOXP3 intron 11 splicing under DDX39B-depleted conditions. In this work we also confirm that introns containing C-rich/U-poor polypyrimidine tract are very sensitive to DDX39B levels. We also observed that cassette exons with C-rich/U-poor py tracts in upstream introns were also sensitive to DDX39B levels and were skipped more upon depletion of DDX39B, but not DDX39A. Among the introns retained more upon DDX39A and DDX39B depletion were DDX39A and DDX39B intron 6, which depend on DDX39A and DDX39B levels, respectively. Therefore, we identified an autoregulatory mechanism through which DDX39A and DDX39B control their respective expression. This study presents evidence that while DDX39A and DDX39B differentially impact certain RNA splicing events, they have many shared targets.
2024-05-29 | GSE253261 | GEO
Project description:Multiple RNA processing events including transcription, mRNA splicing and export are delicately coordinated by the TREX complex. As one of the essential subunits, DDX39B couples the splicing and export machineries by recruiting ALYREF onto mRNA. In this study, we further explore the functions of DDX39B in handling damaged DNA, and unexpectedly find that DDX39B facilitates DNA repair by homologous recombination through upregulating BRCA1. Specifically, DDX39B binds to and stabilizes BRCA1 mRNA. DDX39B ensures ssDNA formation and RAD51 accumulation at DSB sites by maintaining BRCA1 levels. Without DDX39B being present, ovarian cancer cells exhibit hypersensitivity to DNA-damaging chemotherapeutic agents like platinum or PARPi. Moreover, DDX39B-deficient mice show embryonic lethality or developmental retardation, highly reminiscent of those lacking BRCA1. High DDX39B expression is correlated with worse survival in ovarian cancer patients. Thus, DDX39B suppression represents a rational approach for enhancing the efficacy of chemotherapy in BRCA1-proficient ovarian cancers.
2020-08-21 | GSE156543 | GEO
Project description:Purpose: The goal of this study is to investigate the role of DDX39B in RNA splicing Methods: RNA-Seq splicing analysis of HeLa cells with experimentally induced DDX39B expression knockdown
2017-03-28 | GSE94730 | GEO
Project description:Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer. Here we show that DCLK1 expression in the gastric cancer cell line MKN1 impacts EV biogenesis both quantitatively and qualitatively in a kinase dependent manner, revealing a hitherto unknown role for this putative oncogenic kinase. Importantly, the proteome of EVs isolated from DCLK1 expressing gastric cancer cells is enriched for proteins involved in tumor-promoting biological processes, raising the prospect of establishing DCLK1 as a novel anti-cancer target.
2021-03-23 | PXD021371 | Pride