Researchers have focused on the complex molecular and epigenetic pathways that account for the aggressive melanoma spread. Researchers study how the epigenetic silencing of circRNA promotes cancer's growth.
Along with DNA and proteins, RNA is one of the three essential macromolecules necessary for all forms of life.
Three steps make up the general process that all known forms of life have in common. The genetic material from our DNA, which serves as the "blueprint" of the cell, is transformed into an RNA "photocopy," which then contributes in the production of the proteins that the cell needs.
The majority of RNA exists in linear form. However, some RNA molecules are circular. These are known as circular RNAs (circRNA).
Proteins are encoded by linear RNA, but very few circRNAs have known functions. According to the authors of a recent research, the medical profession is just now starting to understand how circRNA affects both healthy physiology and disease.
So what part do circRNAs play in the growth of melanoma? Eva Hernando, Ph.D., a professor in the Department of Pathology at New York University (NYU) Langone Health, and colleagues undertook the investigation.
According to the researchers' findings in their Cancer Cell study, 90% of cancer-related deaths are attributable to metastatic spread, hence the question is important. The critical point at which cancer metastatically spreads can determine a patient's outcome.
Because of its extremely aggressive spread and the fact that metastatic spread can start from primary tumours as small as a few millimetres, melanoma is a useful model for research into the mechanisms behind metastasis.
Genetic errors explain how melanoma cancer cells emerge from normal cells, but DNA errors do not tell the whole story when it comes to explaining how the cancer spreads, say the researchers.
Hernando and colleagues investigated the function of circRNAs in the new study by conducting tests in cell cultures from human melanoma tissues and mice models.
The results indicated that the essential circRNA is called CDR1as. This molecule promotes the spread of cancer when epigenetically silenced, while it prevents the aggressive spread of cancer when activated.
According to the scientists, earlier research has suggested that circRNAs may interact with proteins to connect to RNA and influence cellular processes.
The results of this specific investigation demonstrated that disruption of the connection between CDR1as and one such RNA-attaching protein leads to metastasis. The protein that binds to RNA is known as IGF2BP3.
Hernando and colleagues silenced CDR1as to see how it would affect metastasis. They saw that when CDR1as was switched off, the RNA-binding protein IGF2BP3 roamed freely and promoted metastasis.
IGF2BP3 is connected to CDR1as when it is activated, preventing it from straying to other pro-metastatic proteins.
“We found CDR1as restrains a known pro-cancer protein called IGF2BP3, revealing a new function of CDR1as that may have therapeutic implications,” explains first study author Douglas Hanniford, Ph.D., an instructor in the Department of Pathology at NYU Langone Health.
The team also revealed the epigenetic mechanisms through which CDR1as was silenced and no longer produced in melanoma cells.
Epigenetic changes to genes affect their functioning without altering their DNA code.
“Our study provides new insights into the aggressive behavior of melanoma, and it is the first to expose a circRNA as a suppressor of metastasis.” - Eva Hernando, Ph.D.
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