A team led by researchers at The University of Texas MD Anderson Cancer Center recently revealed the importance of RNA editing in melanoma growth and metastasis. The study was published in the journal Nature Cell Biology and is entitled “Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis.”
Melanoma is the most dangerous form of skin cancer and is caused by damage to the skin cells (usually by ultraviolet radiation from sunshine or tanning beds), which triggers mutations that are not repaired allowing skin cells to rapidly multiply and generate malignant tumors.
Researchers found that RNA editing – a process through which discrete alterations are made to specific nucleotides within the RNA molecule – plays a key role in melanoma development. In its absence, tumors were found to grow and progress.
CREB (cAMP response element-binding protein) is a transcription factor – protein that acts as an on and off switch to regulate genetic instructions – was found to control other transcription factors that are linked to melanoma development. “We found that CREB regulates ADAR1, an enzyme involved in RNA editing,” said the study’s senior author Dr. Menashe Bar-Eli in a news release. “CREB negatively regulated ADAR1, promoting melanoma tumor growth and metastasis.”
“When we discovered that CREB negatively regulated ADAR1, we looked further into how the loss of ADAR1 expression contributes to the cancer spread,” explained Dr. Bar-Eli. The team studied ADAR1 RNA editing function in specific small, non-coding (not translated into proteins) molecules that were found to be associated to several types of cancer; these small molecules are called microRNAs. Three microRNAs were identified as subjected to RNA editing. However, this process was only observed in non-metastatic melanoma cells and not in metastatic cells.
Researchers manipulated microRNAs by suppressing the original microRNA version and overexpressing an “edited” microRNA. “We found that increased wild-type miRNA led to increased tumor growth and cancer spread,” said Dr. Bar-Eli. “In contrast, overexpression of the edited miRNA led to decreased tumor growth and metastasis. The biological functions of edited mi RNAs are different from unedited forms, as they recognize a different set of genes. These results demonstrate a previously unrecognized role for RNA editing in melanoma progression.”