New findings may improve diagnosis and treatment of liver cancer

The study, conducted at Karolinska Institutet, contributes to increased knowledge that could lead to better diagnoses and cancer treatments in the future.

IncRNAs are long non-coding RNA molecules

Our genome supplies the cells of the body with the instructions that determine the highly specialized function of each cell type. Information is transmitted using two different types of RNA molecules: coding RNA, which converts DNA into proteins, and noncoding RNA, which does not produce proteins.

Since non-coding RNA molecules do not produce proteins, not much has been done about them in the past, despite the fact that about 97 percent of the RNA molecules in our bodies are non-coding. However, some proteins, called RNA-binding proteins, have been shown to play an important role in, among other things, cancer because they can affect many different properties of RNA molecules.

It uses CRISPR technology

With the help of tissue material donated by HCC patients, we were able to identify both the coding and non-coding part of our genome to identify RNA-binding proteins that are highly present in HCC cells. We found that many of these proteins interact with a type of long non-coding RNA molecules, called lncRNA, says Claudia Kotter, a researcher in the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and lead author of the study.

The research team conducted a more detailed study of a specific combination of an RNA-binding protein (CCT3) and a lncRNA molecule (LINC00326). Using advanced CRISPR technology, they were able to reduce and increase the amount of protein and lncRNA to see how this affects cancer cells. With the increase of lncRNA, the lipid deposits in cancer cells decreased and the growth of cancer cells slowed down at the same time that a large number of cancer cells died. After studies in a laboratory setting, the results were also confirmed in vivo.

genetically modified with CRISPR–9 . cup It means that it is possible to find genes in a very precise way, removing or adding parts to the DNA of organisms. Part of the complex – enzyme 9 . cup It is the “scissors” that cut the DNA and another part – the RNA – acts as a “title label” and makes the cut take place in the right place.

RNA-based therapy of the future

The researchers’ findings provide insight into the interaction between RNA-binding proteins and lncRNA molecules, and contribute to a better scientific understanding of their role in tumors.

The activities of the CCT3-LINC00326 pair can indeed be used in the diagnosis and prognosis of HCC. Knowing this particular pair is just the beginning and there are many other structures of RNA-binding proteins and lncRNA molecules that we want to investigate further. In the long term, it could contribute to new effective therapies such as RNA-based therapy that focuses on diseased cells only and thus could reduce side effects, says study lead author Jonas Norskov Sondergaard, a researcher in the Kotter research group.

Scientific material:

The CCT3-LINC00326 axis regulates hepatic lipid metabolism, (Jonas Norskov Sondergaard, Christian Sommerauer, Ionot Atanasway, Laura C. Henty, Kee Ging, Julia Gueducci, Lars Protegam, Miriam Owade, Lovorka Stojic, Isabel Barrajan, Claudia Kotter), Gut.

Call:

Claudia Kutter, PhD, Researcher in the Department of Microbiology, Oncology and Cell, Karolinska Institutet, [email protected]

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The research was funded by the Knut and Alice Wallenberg Foundation, Ruth and Richard Julin Foundation, SFO-SciLifeLab Fellowship, Swedish Research Council, Lillian Sagens and Kurt Erickson Research Foundation, Gösta Milton Voluntary Fund, China Grants Council, KI-KID Funding, Swedish Infrastructure National Computing (SNIC), Nilsson-Ehle donations, Barts and London Charity, Cancer Research UK, AIRC Fellowship for Abroad, Stiftelsen Tornspiran and Svenska Läkaresällskapet.