New study identifies previously unknown regulator of melanoma progression
RNA regulator of melanoma could be a new target for cancer therapy
- Date : 18 May 2012
- Topic : Melanoma
In a study published online in Genome Research, researchers have identified a previously unknown non-coding RNA that plays an important role in the biology of melanoma, a finding that could lead to a new target for therapy.
Oncogenes are genes that have the potential to cause cancer, and are often mutated in tumour cells, including melanomas. Mutations in the oncogene BRAF are present in more than 70% of melanomas and the vast majority of BRAF mutants are a single mutant form, BRAFV600E. Inhibitors of BRAFV600E used in the clinic can induce tumour regression, but patients eventually relapse.
Understanding BRAF biology
In order to better understand the biology of oncogenic BRAF and identify new targets for therapy, researchers are investigating the RNAs, the messenger molecules that the cell primarily uses to transmit the information stored in the DNA sequence and translate it into functional proteins. However, about 50% of transcribed RNAs actually code for no proteins at all, but many RNAs may still have critical regulatory roles to play.
In this report, a team of researchers led by Drs. Ross Flockhart and Paul Khavari of the Stanford University School of Medicine has delved into the RNA world of BRAFV600E melanomas by sequencing and analysing the RNA transcriptome of patient samples. They looked for RNA transcripts, including those that may never have been characterised before, that are rewired by BRAFV600E and may be relevant to melanoma.
By digging deeper than ever before, the researchers found more than 100 genes encoding long non-coding RNAs that are dramatically altered by BRAFV600E. Long non-coding RNAs (lncRNAs) are garnering significant interest, as these molecules have been implicated in diverse cellular functions, but the role of lncRNAs in cancer is not well understood.
Of the lncRNAs altered by BRAFV600E, Flockhart and colleagues homed in on a previously uncharacterised lncRNA gene that is recurrently and highly induced in melanomas, called BANCR. Increased activation of the novel gene discovered does not seem to be an isolated event. It will be interesting to investigate if this is also the case in other cancers.
What role BANCR might play in melanoma?
The research team found that by turning off BANCR in the cancer cells by a knockdown technique, the ability of the melanoma cells to migrate in a cell culture experiment was impaired. This indicates that BANCR is required for full migratory capacity in melanoma, and could be a potential target for therapy.
The authors explained that their work illustrates the power of RNA sequencing to study a cancer such as melanoma and identify a previously unknown regulator of disease progression. As studies such as this paint a more complete picture of cancer biology, the scientists will have a better understanding of how tumours evade drugs, and how previously unknown players such as BANCR could be new targets for treatment.
Scientists from the Veterans Affairs Palo Alto Healthcare System and Stanford University contributed to this study. This work was supported by the United States Veterans Affairs Office of Research and Development and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
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