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.
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.
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.
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.