Scientists at The University of Texas MD Anderson Cancer Center have revealed that lack of RNA editing, a process by which information inside RNA molecules is transformed, in melanoma leads to tumor growth and progression through manipulation of proteins.
Study lead Menashe Bar-Eli reported a previously unknown target for CREB (cAMP response element-binding protein), a transcription factor (proteins that turn genetic instructions on and off) that regulates other transcription factors involved in melanoma development. Bar-Eli said, "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."
The research team evaluated the RNA editing functioning of ADAR1 in microRNAs (miRNAs). MiRNAs are small, non-coding molecules that have been linked to several types of cancer. Researchers identified adenosine-to-inosine RNA editing in three microRNAs, and RNA editing occurs only in the non-metastatic (ADAR1-positive), but 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 over-expressing an 'edited' miRNA confirmed the significance of RNA editing in tumor growth and metastasis.
Bar-Eli said, "We found that increased wild-type miRNA led to increased tumor growth and cancer spread. In contrast, over-expression 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."
The study findings appear in 'Nature Cell Biology'.