The link between long noncoding RNAs (lncRNAs) and cancer is known, but clear cancer-associated lncRNAs that are clinically relevant to diagnostics and therapy still need to be established. New findings now identify such biomarkers as well as promising therapy methods that reduce lung tumors in mice. The findings are published today in Nature Communications by a team from University of Gothenburg.
"Higher expression of some of these long noncoding RNA molecules during cell division cycle may cause cells to divide uncontrollably to become cancerous, explains senior co-author Chandrasekhar Kanduri. "This link is known, but no one has made such a broad and extensive analysis previously, nor examined long noncoding RNAs so specifically,"
The team first used nascent RNA capture sequencing to identify 1145 lncRNAs expressed during cellular S-phase. Systematic clinical investigation of various cancer types then revealed 633 independent prognostic markers. In all, 16 different cancer types were covered, including 6,419 solid tumors, and 701 normal tissue controls.
Mouse model experiments were carried out to test the silencing of the most differentially expressed and clinically relevant of these lncRNA markers. Mice xenografted with human lung cancer tissues were injected with lock nucleic acid modified antisense oligonucleotides (LNA-ASO) twice a week. In 15 days, the tumors had decreased in size by almost half.
"Thus we have identified a new method, optimized it in a lab environment, and identified long noncoding RNA molecules that are involved in uncontrolled cell division. By taking aim at these specific molecules, we have reduced cancer growth,” says Kanduri. “Furthermore, the molecules can also be used to predict the disease."
Kanduri and his team stresses the clinical potential of the non-coding RNA approach. "We are proposing that this RNA-based method be used to treat lung cancer, for which the survival rate after five years is currently only 18 percent. We need to conduct more studies to see if there is potential to carry out clinical trials in patients, but we believe there is a future for RNA-based treatment in the treatment of cancer."