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The positionally conserved lncRNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene

ABSTRACT: The positionally conserved lncRNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene

PROVIDER: PRJNA1238859 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32791434_1.fastq.gz	Fastqsanger.gz
	SRR32791434_2.fastq.gz	Fastqsanger.gz
	SRR32791435_1.fastq.gz	Fastqsanger.gz
	SRR32791435_2.fastq.gz	Fastqsanger.gz
	SRR32791436_1.fastq.gz	Fastqsanger.gz

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The syntenic long non-coding RNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene

Project description:Long non-coding RNAs (lncRNAs) play crucial roles in regulating gene expression. Some are essential for organismal development and physiology, and they can contribute to diseases such as cancer. Whilst most lncRNAs exhibit little sequence similarity, conservation of lncRNA transcription relative to neighbouring protein-coding genes suggests potential functional significance. Nevertheless, most positionally equivalent lncRNAs are uncharacterized and it remains unclear whether they exert similar roles in distant species. Here, we identified syntenic melanoma-associated lncRNAs predicted to be components of the MITF gene regulatory network in human melanoma, with positionally equivalent transcripts in zebrafish. Among these, we prioritized Differentiation Antagonizing Non-Protein Coding RNA (DANCR), a cancer-associated lncRNA critical for maintaining somatic progenitor cells in human models, for functional investigation. Dancr is a multi-exonic, cytoplasmically enriched lncRNA transcribed from syntenic regions in the human and zebrafish genomes. MITF and c-MYC, key melanoma transcription factors, regulate human DANCR expression and melanoma patients with high DANCR display significantly decreased survival. DANCR is a melanoma oncogene that controls cancer-associated gene expression networks and promotes human melanoma cell proliferation and migration. Zebrafish dancr is dynamically expressed across multiple different cell types in the developing embryo, regulates genes involved in cell death, and is essential for embryonic development. Our work suggests that cancer-critical lncRNAs such as Dancr, expressed from similar regions in vertebrate genomes, may regulate related genes and processes involved in both embryonic development and tumorigenesis across species.

2025-03-25 | GSE292491 | GEO

The syntenic lncRNA DANCR is a human melanoma oncogene and an essential regulator of zebrafish development

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The syntenic lncRNA DANCR is a human melanoma oncogene and an essential regulator of zebrafish development

Project description:The syntenic lncRNA DANCR is a human melanoma oncogene and an essential regulator of zebrafish development

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RNA-seq in SUNE-1 cells after downregulation of DANCR expression

Project description:To explore whether DANCR plays a role in nasopharyngeal carcinoma tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of DANCR siRNA and control groups.

2019-07-20 | GSE117415 | GEO

Altered expression of genes in DANCR knockdown bladder cancer cells

Project description:The prognosis for bladder cancer (BCa) patients with lymph node (LN) metastasis is forlorn and restrainedly improved by current treatment. DANCR is reported to play a role in prostate cancer and liver cancer. However, its function and underlying mechanism in BCa remains unknown. The goal of this study is to identify the target genes of DANCR in bladder cancer. Our results indicate that the genes regulated by DANCR are involved in a variety of biological functions, such as proliferation and metastasis.

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Project description:Expression profiling by array Effects of DANCR siRNA on gene expression

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Expression data from second oncogene expressing Melanoma Cells.

Project description:Expression data from second oncogene expressing Melanoma Cells.

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Altered expression of genes in DANCR knockdown bladder cancer cells

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Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish.

Project description:The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo.

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Bmp8a is an essential positive regulator of antiviral immunity in zebrafish.

Project description:Bone morphogenetic protein (BMP) is a kind of classical multi-functional growth factor that plays a vital role in the formation and maintenance of bone, cartilage, muscle, blood vessels, and the regulation of adipogenesis and thermogenesis. However, understanding of the role of BMPs in antiviral immunity is still limited. Here we demonstrate that Bmp8a is a newly-identified positive regulator for antiviral immune responses. The bmp8a-/- zebrafish, when infected with viruses, show reduced antiviral immunity and increased viral load and mortality. We also show for the first time that Bmp8a interacts with Alk6a, which promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, and induces the production of type I interferons (IFNs) in response to viral infection. Our study uncovers a previously unrecognized role of Bmp8a in regulation of antiviral immune responses and provides a target for controlling viral infection.

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