Neuroendocrine tumors, including small cell lung cancer and neuroendocrine prostate cancer, are very aggressive with high chances of spreading. However, many individuals develop resistance to few available treatment options, leading to poor patient outcomes. Researchers are therefore aiming to develop new therapeutic methods that focus on the disease-specific molecular mechanisms of these tumors.
In a recent article published in Molecular Therapy: Nucleic Acids , a team of researchers at Osaka University describe a strategy targeting one such mechanism, called RNA splicing. RNA splicing is the process by which cells remove certain portions of messenger RNA (mRNA) molecules. This produces the mature mRNA that contains the instructions for making a protein for a specific gene.
Because incorrect RNA splicing can result in dysfunctional or overactive proteins, this process can significantly contribute to disease development. The team focused on a protein named the RE1-silencing transcription factor (REST), which typically represses certain genes that support neuroendocrine phenotypes. Interestingly, an abnormally spliced form of REST mRNA is expressed at high levels in neuroendocrine tumors.
Incorrect splicing of REST mRNA can cause the resulting protein to lose its function, which can lead to neuroendocrine cancer development. Our group aimed to develop a molecular method that could be used to correct REST splicing patterns." Keishiro Mishima, lead author of the study The team u.