Long non-coding RNA melanoma markers
Research type
Research Study
Full title
Identification of novel long non-coding RNA prognostic markers and therapeutic targets for melanoma
IRAS ID
191750
Contact name
Keith Vance
Contact email
Sponsor organisation
University of Bath
Clinicaltrials.gov Identifier
Not applicable, Not applicable
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Research Summary
Malignant melanoma is a highly aggressive type of skin cancer. In the UK, the incidence rate of melanoma is rising rapidly and more than 2,000 people currently die each year from the disease. Novel prognostic markers and therapeutic options for melanoma are greatly needed. In this proposal, we aim to investigate long sequences of non-coding RNA (lncRNA). There is increasing evidence that these lncRNA may be a potential target in cancer treatment. Aberrant lncRNA expression has been shown to be associated with particularly aggressive disease in a number of different cancer types. In preliminary experiments, we have assembled a new dataset of 1538 melanoma expressed lncRNAs that are targets for regulation by MITF (microphthalmia-associated transcription factor), a critical transcriptional regulator of melanoma growth and metastasis, two important hallmarks of cancer. From this, we have identified a prioritised subset of 10 putative lncRNA drivers of melanoma that are highly expressed in melanoma cell lines compared to immortalized human melanocytes. The expression of these lncRNAs will be profiled across a panel of normal melanocytic nevi as well as low and high risk primary melanoma patient tissue. We will identify lncRNAs that are mis-expressed in melanoma patients and test whether these lncRNAs can be used to predict recurrence and metastatic potential in primary tumours. We will investigate the function of a subset of these lncRNAs in the control of melanoma growth and invasion using cell lines in culture. LncRNA regulators of melanoma identified here represent novel candidate therapeutic targets whose function could be disrupted in future new melanoma treatments.
Summary of Results
We attempted to profile the expression of a prioritised subset of long noncoding RNAs (lncRNAs) across a panel of normal melanocytic nevi as well as low and high risk primary melanoma patient tissue. These lncRNAs are regulated by MITF, a key melanoma oncogene, and are predicted to represent candidate new melanoma biomarkers and therapeutic targets whose function could be disrupted in future new melanoma treatments. LncRNAs are in general expressed in a cell subtype specific manner and at low levels. Unfortunately, we were unable to extract high enough quality RNA from paraffin-embedded melanoma tissue to reproducibly detect lncRNA expression and were unable to proceed as planned. We instead made use of publicly available RNA-seq data and associated clinical information in The Cancer Genome Atlas to identify lncRNA expression in different melanoma subtypes and stages and to predict risk.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
16/EM/0151
Date of REC Opinion
6 Apr 2016
REC opinion
Favourable Opinion