A recent study from MIT researchers published in eLife journal showed that a type of RNA-binding protein known as Musashi proteins, are involved in breast cancer regulation by increasing the proliferation rate of cancer cells.
Previous studies had already demonstrated that this type of transformation was tightly regulated by transcription factors. However, this new study demonstrates that RNA-binding proteins, which can impact gene expression through messenger RNA regulation, also play a key role in this process.
“Recent discoveries show that there’s a lot of RNA-processing that happens in human cells and mammalian cells in general,” lead author Yarden Katz, PhD, said in an MIT news release. “RNA is processed at several points within the cell, and this gives opportunities for RNA-binding proteins to regulate RNA at each point. We’re very interested in trying to understand this unexplored class of RNA-binding proteins and how they regulate cell-state transitions.”
Not much was known regarding the biological functions of Musashi proteins, which until this study, had been used to identify neural stem cells and were found to be present in some types of cancer, including glioblastoma, a severe form of brain cancer.
“Normally they’re marking stem and progenitor cells, but they get turned on in cancers. That was intriguing to us because it suggested they might impose a more undifferentiated state on cancer cells,” Dr. Katz added.
The team used neural stem cells to understand the effect of Musashi proteins on other genes, observing that genes directly influenced by different levels of these proteins were linked to epithelial-to-mesenchymal transition (EMT), a process that allows cancer cells to metastasize throughout the body. Furthermore, the team found that Musashi proteins are expressed at high levels in a type of breast tumors, luminal B tumors.
Researchers were able to preform in vitro knockdowns of Musashi proteins in breast cancer cells, showing this procedure forced the cells to transition out of their epithelial state. This means that Musashi proteins are a key factor for sustaining cancer cells in a proliferative, epithelial state.
“These proteins seem to really be regulating this cell-state transition, which we know from other studies is very important, especially in breast cancer,” Dr. Katz added.
Researchers found that the mechanisms behind this process included a gene called Jagged1 that regulates the Notch signaling pathway, involved in cellular proliferation.
“Musashi proteins have been known to be interesting for many years, but until now nobody has really figured out exactly what they’re doing, especially on a genome-wide scale,” Brenton Graveley, a professor of genetics and developmental biology at the University of Connecticut, said in the press release.