RNA regulator of melanoma could be a new target for cancer therapy

May 10, 2012

Melanoma is the most deadly form of skin cancer, estimated by the National Cancer Institute to afflict more than 70,000 people in the United States annually and the incidence rate continues to rise. 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.

Most skin cancers are nonmelanomas, arising from cells other than melanocytes (the melanin-producing cells that are responsible for a suntan). Melanomas, skin cancers that arise from melanocytes, are less common but more dangerous because they can migrate deep into the skin to find blood and that help the tumor cells to grow and spread to other parts of the body.

Oncogenes are genes that have the potential to cause cancer, and are often mutated in , including melanomas. Mutations in the oncogene 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 , but patients eventually relapse.

In order to better understand the biology of oncogenic BRAF and identify new targets for therapy, researchers are investigating the RNA world of cancer. RNAs are the that the cell primarily uses to transmit the information stored in the DNA sequence, and translate it into . 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 analyzing the RNA "transcriptome" of patient samples. They looked for , including those that may never have been characterized before, that are rewired by BRAFV600E and may be relevant to melanoma.

"By digging deeper than ever before, we found more than 100 genes encoding long non-coding RNAs that are dramatically altered by BRAFV600E," said Flockhart. 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 uncharacterized lncRNA gene that is recurrently and highly induced in melanomas, called BANCR. "Increased activation of the novel gene we discovered does not seem to be an isolated event," Flockhart noted. "It will be interesting to investigate if this is also the case in other cancers."

To test what role BANCR might be playing in melanoma, the team found that by turning off BANCR in the cancer cell by a technique called knockdown, 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, we will have a better understanding of how tumors evade drugs, and how previously unknown players such as BANCR could be new targets for treatment.

Explore further: RNA spurs melanoma development

More information: Flockhart RJ, Webster DE, Qu K, Mascarenhas N, Kovalski J, Kretz M, Khavari PA. BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration. Genome Res doi: 10.1101/gr.140061.112

Related Stories

RNA spurs melanoma development

May 10, 2011
Traditionally, RNA was mostly known as the messenger molecule that carries protein-making instructions from a cell's nucleus to the cytoplasm. But scientists now estimate that approximately 97 percent of human RNA doesn't ...

Second mutation in BRAF-mutated melanoma doesn't contribute to resistance

April 1, 2012
A second mutation found in the tumors of patients with BRAF-mutated metastatic melanoma does not contribute to resistance to BRAF inhibitor drugs, a finding that runs counter to what scientists expected to be true.

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.