Discovering new cancer treatments in the dark matter of the human genome

Cancer is in Switzerland the second leading cause of death. Among the different types of cancers, non-small cell lung cancer (NSCLC) kills the most patients and remains largely incurable. Unfortunately, even newly approved therapies can extend the life of patients only by a few months and only few survive the metastatic stadium long-term. Thus, new treatments which attack the cancer in novel ways are sought. In a recently published study in the Journal Cell Genomics, researchers of the University of Bern and the Insel Hospital determined new targets for drug development for this cancer type.

The Dark Matter of the genome

For new targets, they looked at the poorly-understood class of genes called “long noncoding RNAs (Ribonucleic acids)” (lncRNAs). LncRNAs exist in abundance in the so-called “Dark Matter” or non-protein-coding DNA that constitutes the vast majority of our genome. The human genome contains around 20,000 “classical” protein-coding genes, but this number is dwarfed by 100,000 lncRNAs. Of 99% of lncRNAs the biological functions are unknown.

As the name long noncoding RNAs implies, unlike messenger RNAs (mRNAs), they do not encode the construction plans for proteins. Like for mRNAs, the building instructions for lncRNAs are contained in the cell’s DNA.

New tool determines potential targets

To study the role of lncRNAs in NSCLC, the researchers started by analyzing publicly available datasets to see which lncRNAs are present in NSCLC. This analysis led to a list of over 800 lnRNAs, whose importance for NSCLC cells the researchers wished to investigate. For this investigation, they developed a screening system which prevents the production of the selected lncRNAs by deleting part of their construction instructions in the DNA.

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