New findings could contribute to better diagnosis and treatment of liver cancer – ScienceDaily
In a new study, researchers at Karolinska Institutet have identified the presence of a specific connection between a protein and an ncRNA molecule in liver cancer. By increasing the presence of the ncRNA molecule, the fat deposits of the tumor cell decrease, which causes the tumor cells to stop dividing, and they eventually die. The study, published in the journal Intestine, contributes to increased knowledge that can contribute to better diagnosis and future treatments for cancer.
Our genome gives our cells instructions that determine the highly specialized function of each type of cell. Information is sent using two different types of RNA molecules: coding RNA which converts DNA into proteins and non-coding RNA which does not produce proteins.
Since non-coding RNA molecules do not produce proteins, they have not been the main subject of research in the past, even though they make up about 97% of the RNA in our bodies. However, certain proteins, called RNA binding proteins, have been shown to play a crucial role in cancer due to their ability to affect several different properties of RNA molecules.
“With the help of tissue material donated by liver cancer patients, we were able to map both the coding and non-coding part of our genome to identify RNA-binding proteins that have a strong presence in liver cancer cells ”, explains the lead author of the study, Claudia Kutter, researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. “We found that many of these proteins interacted with a long type of non-coding RNA molecules called lncRNA.”
The research team conducted a more detailed study of a specific pairing of an RNA binding protein (CCT3) and an ncRNA molecule (LINC00326). Using advanced CRISPR technology, they were able to both reduce and increase the amount of protein and ncRNA to see how it affected cancer cells. When the lncRNA increased, the fat deposits of the tumor cell decreased, cell division ceased, and many cancer cells died. Following laboratory studies, the results were also verified in vivo.
Many more combinations to study
The researchers’ discovery provides insight into the interaction between RNA binding proteins and ncRNA molecules, and contributes to a better scientific understanding of their role in tumors.
“The activities of the CCT3-LINC00326 pair may already be used in the diagnosis and prognosis of liver cancer,” says the study’s first author, Jonas Nørskov Søndergaard, a researcher in the Kutter research group. “However, knowing this particular pairing is just the beginning and there are many other combinations of RNA binding proteins and ncRNA molecules that we will study further. In the long term, these findings may help contribute to new effective treatments such as RNA-based treatments that target only diseased cells, with the possibility of reducing side effects. ”
The study was funded by grants from the Knut and Alice Wallenberg Foundation, the Ruth and Richard Julin Foundation, an SFO-SciLifeLab Fellowship, the Swedish Research Council, the Lillian Sagen and Curt Ericsson Research Foundation , Gösta Miltons Foundation, China Scholarship Council, KI-KID Funding, SNIC projects, Nilsson-Ehle Endowments, Barts and London Charity, Cancer Research UK, AIRC Fellowship for Abroad, Tornspiran Foundation and the Swedish Society of Medicine.