The positionally conserved lncRNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene
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PROVIDER: PRJNA1238859 | ENA |
REPOSITORIES: ENA
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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
Project description:Expression profiling by array Effects of DANCR siRNA on gene expression
2016-12-05 | GSE76176 | GEO
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
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.
2019-09-01 | GSE119639 | GEO
Project description:Background and aim: As an oncogenic long noncoding RNA, differentiation antagonizing non-protein coding RNA (DANCR) was identified in many kinds of cancers. However, the specific function of DANCR in melanoma remains unclear. Here, we aimed to clarify the role of DANCR played in melanoma progression and the underlying mechanisms. Methods: TCGA data base and patients' tissue samples were used to analyzed the function of DANCR in melanoma progression. Transwell assay was used to detect cell migration and tube formation assay was employed to assess the ability of angiogenesis. Western blot, qRT-PCR, ELISA and IHC assay were used to examine VEGFB expression and secrection. Luciferase assay verified the binding of DANCR and miRNA. Results: We found that the expression of DANCR was positively related to poor clinical prognosis of melanoma. DANCR knockdown suppressed melanoma progression with a more significant suppression in vivo compared with it in vitro. Further detection showed that beyond promoting proliferation, DANCR also enhanced angiogenesis via upregulating VEGFB. Mechanistic analysis revealed that DANCR upregulating VEGFB through sponging miR-5194, which negatively regulated VEGFB expression and secretion. Conclusion: We demonstrated a novel oncogenic role DANCR played in melanoma and suggested a new avenue for melanoma therapy by targeting the DANCR/miR-5194/VEGFB signaling.
| S-EPMC10197948 | biostudies-literature
Project description:A conserved microRNA signature related to cellular transformation by the RAS oncogene
| PRJNA208859 | ENA
Project description:A conserved microRNA signature related to cellular transformation by the RAS oncogene (miRNA)
| PRJNA208860 | ENA
Project description:Sustained hepatic inflammation can contribute to cancer initiation and progression via tumor-initiating cell expansion, but underlying mechanisms remains unknown. Expression profiles of lncRNAs/mRNAs were measured in normal, chronic hepatitis, cirrhotic and cancerous livers. We found abundant disease-related lncRNAs/mRNAs deregulated across different stages of inflammation-triggered liver disease and refined a transformation gene signature to distinguish pathological liver tissues. Amongst this signature, a conserved lncRNA DANCR was silenced in normal adult liver, but overexpressed in fetal and cancerous livers. Remarkably, increased DANCR significantly correlates with poor prognosis in multiple-center cohorts and is directly induced by inflammatory pathways including NF-κB and STAT3. DANCR could suppress cell differentiation and drive expansion of tumor-initiating cells, leading to chemoresistance. Moreover, in vitro and in vivo inhibition confirms the significance of DANCR as a therapeutic target when combined with other chemotherapy. We illustrate the role of DANCR relies on the regulation of CTNNB1 in a novel miRNA-blocking manner. Our studies reveal the expression of lncRNAs/mRNAs in normal and pathological livers and suggest the importance of oncofetal lncRNA DANCR in inflammation-induced malignant transformation, offering a potential prognostic marker and a therapeutic target for HCC. In the study, 10 normal livers (NL), 10 chronic inflammatory livers (IL), 10 cirrhotic livers (CL), 13 early HCC (eHCC) and 13 advanced HCC (aHCC) samples were profiled their lncRNA/mRNA expression
2014-01-22 | E-GEOD-54238 | biostudies-arrayexpress
Project description:A conserved microRNA signature related to cellular transformation by the RAS oncogene (Affymetrix mRNA)
| PRJNA198656 | ENA
Project description:BackgroundLong noncoding RNAs (lncRNAs) are a new class of cancer regulators. Here, we aimed to investigate the diagnostic and therapeutic values of an lncRNA, differentiation antagonizing noncoding RNA (DANCR), in lung cancer.MethodsReal-time polymerase chain reaction was used to compare DANCR levels in normal and cancerous lung tissues as well as lung cancer cells. Lentiviral transduction was used to induce DANCR overexpression or silencing in vitro, followed by monitoring cell proliferation, colony formation, and changes in microRNA-216a (miR-216a) expression. DANCR-specific small hairpin RNA transduction was used to establish cells with stable DANCR knockdown, and silenced cells were used to initiate lung tumor xenografts, followed by monitoring tumor growth.ResultsDANCR upregulation was seen in lung cancer, particularly in high-grade lung cancer tissues and aggressive cancer cells. Ectopic DANCR expression induced lung cancer cell proliferation and colony formation, whereas DANCR silencing induced opposing effects. The miR-216a level in cancer cells was negatively correlated with DANCR expression. The DANCR knockdown reduced the growth of tumor xenografts in vivo.ConclusionDANCR upregulation is a potential indicator of aggressive lung cancer. Silencing of DANCR has great potential as a potent therapeutic strategy in lung cancer.
| S-EPMC6852365 | biostudies-literature