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Study Shows Lack of RNA Editing Leads to Melanoma Growth and Metastasis

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Key Points

  • Researchers found CREB regulates ADAR1, an enzyme involved in RNA editing.
  • RNA editing occurs only in non-metastatic melanoma cells (ADAR1-positive), not in metastatic melanoma cells (ADAR1-negative).
  • Increased wild-type miRNA led to increased tumor growth and cancer spread.

In a new study reported by Shoshan et al in Nature Cell Biology, researchers at The University of Texas MD Anderson Cancer Center established a link between melanoma and lack of RNA editing, which leads to tumor growth and progression through manipulation of proteins.

Study Findings

Study lead Menashe Bar-Eli, PhD, Professor of Cancer Biology at MD Anderson, reported a previously unknown target for CREB (cAMP response element-binding protein), a transcription factor that regulates other transcription factors involved in melanoma development.

“We found that CREB regulates ADAR1, an enzyme involved in RNA editing,” said Dr. Bar-Eli. “CREB negatively regulated ADAR1, promoting melanoma tumor growth and metastasis…we [then] looked further into how the loss of ADAR1 expression contributes to cancer spread.”

Dr. Bar-Eli and colleagues evaluated the RNA editing functioning of ADAR1 in microRNAs (miRNAs). MicroRNAs are small, non-coding molecules that have been linked to several types of cancer. Dr. Bar-Eli identified adenosine-to-inosine RNA editing in three miRNAs. RNA editing occurs only in the nonmetastatic melanoma cells (ADAR1-positive), not in the metastatic melanoma cells (ADAR1-negative).

Manipulation of the miRNAs, by silencing the naturally occurring or wild-type version of a miRNA and overexpressing an “edited” miRNA, confirmed the significance of RNA editing in tumor growth and metastasis.

miRNA, Tumor Growth, and Cancer Spread

“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 miRNAs 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."

The team's investigation involved study of cell lines, mice, and data from The Cancer Genome Atlas (TCGA).

Dr. Bar-Eli is the corresponding author for the Nature Cell Biology article.

This study was supported by the National Institutes of Health, an MD Anderson Cancer Center grant, and MD Anderson's Sister Institute Network Fund. For full disclosures of the study authors, visit http://www.nature.com/ncb/index.html

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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