Long non-coding RNA expression profile of primary melanoma versus nevi
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE183878 | GEO | 2021/12/23
REPOSITORIES: GEO
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Project description:Long non-coding RNA expression profile of primary melanoma versus nevi
| PRJNA762264 | ENA
Project description:A substantial part of cutaneous malignant melanomas develops from benign nevi. However, the precise molecular events driving the transformation from benign to malignant melanoma are not well understood. We used laser microdissection and mass spectrometry to analyze the proteomes of melanoma subtypes, including superficial spreading melanomas (SSM, n=17), nodular melanomas (NM, n=17), and acral melanomas (AM, n=15). Furthermore, we compared the proteomes of nevi cells and melanoma cells within the same specimens (nevus-associated melanoma (NAM, n=14)). In total, we quantified 7,935 proteins. Despite the genomic and clinical differences of the melanoma subtypes, our analysis revealed relatively similar proteomes, except for the upregulation of proteins involved in immune activation in NM vs AM. Examining NAM versus nevi, we found 1,725 differentially expressed proteins. Among these proteins were 140 that overlapped with cancer hallmarks, tumor suppressors, and regulators of metabolism and cell cycle. Pathway analysis indicated aberrant activation of the RAS/MAPK and PI3K-AKT-mTOR pathways, as well as the Hippo-YAP pathway. Using a classifier, we identified six proteins capable of distinguishing melanoma from nevi samples. Our study represents the first comprehensive comparative analysis of the proteome in melanoma subtypes and associated nevi, offering new insights into the biological behavior of these distinct entities.
2024-01-28 | PXD044107 | Pride
Project description:The MITF and SOX10 transcription factors regulate the expression of genes important for melanoma proliferation, invasion and metastasis. Despite growing evidence of the contribution of long non-coding RNAs (lncRNAs) in melanoma and other cancers, their functions within MITF-SOX10 transcriptional programmes is poorly investigated. Here, we identify 245 candidate melanoma associated lncRNAs whose loci are co-occupied by MITF-SOX10 and are enriched at active enhancer-like regions. We characterise the function and molecular mechanism of action of one of these lncRNAs, Disrupted In Renal Carcinoma 3 (DIRC3), and show that it operates as a MITF-SOX10 regulated tumour suppressor. DIRC3 depletion in human melanoma cells leads to increased anchorage-independent growth, a hallmark of malignant transformation, whilst melanoma patients classified by low DIRC3 expression have decreased survival. DIRC3 is a nuclear lncRNA that functions locally to activate expression of its neighbouring IGFBP5 tumour suppressor through modulation of chromatin structure and suppression of SOX10 binding to putative regulatory elements within the DIRC3 locus. In turn, DIRC3 dependent regulation of IGFBP5 impacts the expression of genes important for cell metabolism, oxidative phosphorylation and cancer. Our work indicates that lncRNA components of MITF-SOX10 networks are an important new class of melanoma regulators and candidate therapeutic targets.
2019-11-11 | GSE129078 | GEO
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:SLNCR is a long non-coding RNA that promotes melanoma formation. Previously, we have shown that SLNCR regulates gene expression and melanomagenesis via interacting with different transcription factors. Here we show that SLNCR is associated with several genomic sites that contain RNA: DNA triplex target sites (TTSs). The primary sequence of SLNCR contains 4 triplex forming regions (TFRs), which are homologous to the TFRs of MEG3, HOTAIR, and PARTICLE lncRNAs. Full-length SLNCR overexpression promotes proliferation, migration, and invasion of melanoma cells and induces characteristic gene expression changes that are reversed by deletions of TFS-1, -2, -4, or -5. These triplex-dependent genes are enriched in pathways involved in cell cycle regulation and cell migration. We directly demonstrate that SLNCR TFRs can form RNA•DNA-DNA triplexes with the TTSs in promoters of genes, suggesting network level gene regulation. Finally, inhibitory oligos that block SLNCR•DNA-DNA triplex formation reversed the effect of SLNCR-mediated migration and proliferation ex vivo demonstrating that triplex formation might play a role in driving melanoma progression.
2026-05-26 | GSE302468 | GEO
Project description:We sought to identify genes and gene signatures which correlate with progression by sampling human melanomas from nevi, primary, and metastatic tumors. The large number of samples also permits analysis within groups. Human melanoma samples were isolated from historical frozen patient specimens. RNA was extracted and run on the human Affymetrix U133A microarray chip.
2013-05-01 | E-GEOD-46517 | biostudies-arrayexpress
Project description:Approximately one-third of melanomas arise from benign nevi, yet the transcriptional and microenvironmental changes accompanying this transition remain incompletely understood. To study the nevus-to-melanoma transition, we employed genome-wide spatial transcriptomics combined with imaging mass cytometry on adjacent nevus-melanoma lesions.
2026-06-02 | GSE298774 | GEO
Project description:Distinguishing between Spitz nevus and melanoma presents a challenging task for clinicians and pathologists. Most of these lesions are submitted entirely in formalin for histologic analysis by conventional hematoxylin and eosin-stained sections, and fresh-frozen material for ancillary studies is rarely collected. Molecular techniques, such as comparative genomic hybridization (CGH), can detect chromosomal alterations in tumor DNA that differ between these 2 lesions. This study investigated the ability of high-resolution array-based CGH to serve as a diagnostic test in distinguishing Spitz nevus and melanoma using DNA isolated from formalin-fixed and paraffin-embedded samples. Two of 3 Spitz nevi exhibited no significant chromosomal alterations, while the third showed gain of the short arm of chromosome 11p. The latter finding has previously been described as characteristic of a subset of Spitz nevi. The 2 melanomas showed multiple copy number alterations characteristic of melanoma such as 1q amplification and chromosome 9 deletion. This study has shown the utility of array-based CGH as a potential molecular test in distinguishing Spitz nevus from melanoma. The assay is capable of using archival paraffin-embedded, formalin-fixed material; is technically easier to perform as compared with conventional CGH; is more sensitive than conventional CGH in being able to detect focal alterations; and can detect copy number alterations even with relatively small amounts of lesional tissue as is typical of many skin tumors. Series_type = clinical_history_design A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Keywords: other
2005-02-09 | GSE1755 | GEO
Project description:Focal amplifications of 3p13-3p14 occur in about 10% of melanoma and are associated with poor prognosis. The melanoma-specific oncogene MITF resides at the epicenter of this amplicon1 . However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA gene LINC01212 is consistently cogained with MITF. In addition to being amplified, LINC01212 is a target of the lineage-specific transcription factor SOX10 and, consequently, it is expressed in more than 90% of human melanomas, but not in normal adult tissues. Whereas exogenous LINC01212 functions in trans to increase melanoma clonogenic potential, LINC01212 knock-down drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state, BRAF, NRAS or TP53 status and increases their sensitivity to MAPK-targeting therapeutics both in vitro and in Patient-Derived Xenograft (PDX) models. Mechanistically, LINC01212 interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that targeting the lineage addiction oncogene LINC01212, especially in combination with BRAFV600Einhibitors, disrupts vital mitochondrial functions in a cancer-cell specific manner and is therefore expected to deliver highly effective and tissuerestricted anti-melanoma therapeutic responses.
2016-01-13 | PXD002565 | Pride
Project description:Despite malignant cutaneous melanoma is relatively rare compared to other skin cancers, it is still responsible for 80% of all skin cancer-related deaths. To identify molecular signatures of melanoma progression, excisional biopsies from 18 common melanocytic nevi (CMN), 8 primary radial growth phase melanomas (RGPM), 15 primary vertical growth phase melanomas (VGPM) and 5 melanoma metastases (MTS) were profiled using whole genome oligo-microarrays. Differentially expressed genes for each progression step were identified, and validation of selected transcripts by qRT-PCR was performed on an independent cohort of fixed samples. The comparison between CMN and RGPM showed an enrichment of Gene Ontology (GO) terms related to inter and intra-cellular junctions, whereas the transition from RGPM to VGPM was characterized by the deregulation of WNT3, MAPK and AKT pathways. In this step, enrichment analysis underlined the alteration of biological processes linked to apoptosis. Upregulation of genes involved into DNA double-strand breaks repair and downregulation of cellular adhesion genes were observed in MTS respect to VGPM. Futhermore, the gene expression profiles of 11 dysplastic nevi (DN) were compared to all the others. Some genes controlling proliferation were found more expressed than in CMN. Overall, DN displayed an heterogeneous behaviour, with relevant oncogenes, such as MYC and BCL6, less expressed than in RGPM, and a modulation pattern similar to VGPM for a subset of gene families, such as mismatch repair. This suggests that DN is not an intermediate step within melanoma progression, but a separate entity with an independent risk of progression to melanoma Keywords: Melanoma progression, gene expression profiling, qPCR
2009-09-30 | GSE12391 | GEO