Cancer cell: circular RNA limits the metastasis of skin cancer

February 24, 2020 / BIOON / - a new study found that a mysterious genetic material can inhibit the spread of skin cancer cells, but as they mature, the material is often lost The new study was recently published in cancer cell In general, DNA is transformed into RNA and then into proteins with cellular functions Although most RNAs are linear molecules, some form circles when their ends loop and attach The authors of the study say that circular RNA does not encode proteins, but is part of a complex regulatory system, but its function is still unclear Photo source: cancer cell's study in cell culture and mice, led by researchers from NYU Grossman School of medicine, is the first to show that a circular RNA called cdr1as can prevent the malignant spread of melanoma, and its absence can promote the spread A study of human melanoma also showed that the increase of cdr1as level was related to the increase of survival rate Melanoma is the most lethal form of skin cancer The aggressive spread or metastasis of cancer cells is the main cause of death of melanoma patients Cancer cells are produced from normal cells due to genetic errors, but changes in DNA do not fully explain how cells spread "Our study provides new insights into the invasive behavior of melanoma and for the first time reveals the role of circrna as a transfer inhibitor," said Dr EVA Hernando, senior author of the study and associate professor of pathology at the Langone health center at New York University "We found that cdr1as inhibits IGF2BP3, a known carcinogenic protein, which reveals a new function of cdr1as and may have therapeutic significance," added Dr Douglas hanniford, lead author of the study Recent studies have shown that circular RNAs have previously unknown functions, including their binding to proteins attached to RNA, thus affecting cell function Specifically, this new study shows that when the interaction between cdr1as and RNA binding protein IGF2BP3 is destroyed, melanoma metastasis begins If cdr1as is active, the IGF2BP3 protein binds to its circular RNA molecule, rather than to other RNA encoding the transfer promoting protein, the researchers said When using molecular technology to remove cdr1as, IGF2BP3 can promote the invasion of cancer cells, which occurs when cells penetrate the skin layer and spread to distant organs This study identified the source of cdr1as in cells as linc00632, another type of RNA known as long-chain noncoding RNA The experiment further revealed that an "epigenetic" mechanism in melanoma cells silenced linc00632 gene, thus stopping the production of cdr1as Epigenetic changes regulate gene operation without changing the DNA code, the researchers said Among them is a molecule called methyl attached to histones, which are "spools" around DNA chains Methylation determines whether a given piece of DNA can be untangled and acquired, or whether it can be compressed instead to keep the gene silent This new study found that a special histone methylation, H3K27me3, can inhibit the start of proliferation of linc00632 gene in melanoma cells, which are already lack of cdr1as The authors say this interaction may represent a mechanism that helps cells migrate during normal (fetal) development, but can lead to cancer spread when it happens again in the tumor by mistake (BIOON Com) reference: EVA Hernando et al Epigenetic silencing of cdr1as drives IGF2BP3 mediated melanoma invasion and metastasis Cancer cell (2020) Doi: https://doi.org/10.1016/j.ccell.2019.12.007