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Series GSE129078 Query DataSets for GSE129078
Status Public on Nov 11, 2019
Title The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design 2 melanoma and 1 melanocyte cell lines were subjected to
Contributor(s) Louphrasitthiphol P, Goding CR
Citation(s) 31881017
Submission date Mar 29, 2019
Last update date Jan 14, 2020
Contact name Pakavarin Louphrasitthiphol
Phone 01865 617543
Organization name Ludwig Institute for Cancer Research
Department Nuffield Department of Clinical Medicine
Lab Prof. CRGoding
Street address Old Road Campus Research Building (off Roosevelt Drive)
City Oxford
ZIP/Postal code OX3 7DQ
Country United Kingdom
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (3)
GSM3693028 IGR37
GSM3693029 IGR39
BioProject PRJNA529912
SRA SRP189902

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE129078_RAW.tar 3.0 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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