Lack of RNA Editing Spurs Melanoma Growth

Scientists have discovered that a lack of RNA editing in melanoma results to tumor growth and progression through protein manipulation.

Published in Nature Cell Biology, the study, led by Menashe Bar-Eli, PhD, professor of Cancer Biology, at The University of Texas MD Anderson Cancer Center, reported a previously unknown target for CREB (cAMP response element-binding protein), a transcription factor regulating other transcription factors involved in melanoma development.

Their investigation involved study of cell lines, mice, and data from The Cancer Genome Atlas (TCGA). The TCGA is a research program supported by the National Cancer Institute and National Human Genome Research Institute within the National Institutes of Health.

The team evaluated the RNA editing function of ADAR1 in microRNAs (miRNAs), non-coding molecules that have been linked to several types of cancer and identified adenosine-to-inosine RNA editing in 3 miRNAs. RNA editing occurs only in the non-metastatic cells (ADAR1-positive), but not in the metastatic melanoma cells (ADAR1-negative).

Bar-Eli commented, "We found that CREB regulates ADAR1, an enzyme involved in RNA editing. 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."

Bar-Eli’s team realized that silencing the naturally occurring version of a miRNA and overexpressing an "edited" miRNA confirmed the significance of RNA editing in tumor growth.

"We found that increased wild-type miRNA led to increased tumor growth and cancer spread," said 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."