Prostate cancer, discovered mechanism that favors it: Italian study

Research conducted by the Catholic University of Rome in collaboration with the University of Tor Vergata

Discovered a molecular mechanism that favors the development of prostate cancer and which, if defused, allows the growth of cancer cells to be stopped. The authors of the research – which could pave the way for new therapeutic approaches – are scientists from the Catholic University Campus of Rome, in collaboration with the Tor Vergata University of Rome. At the center of this oncogenic action mechanism, described in the journal ‘Nature structural & molecular biology’, there are two molecules, called Sam68 and XRN2 which sit on messenger RNAs (molecules which contain the genetic code for protein synthesis, the same used at the base of the anti-Covid vaccines) and make them more efficient, thus promoting the proliferation of prostate cells.

“It was already known that tumors in general, and prostate cancer in particular, have messenger RNAs with shorter regulatory regions, and that this feature is associated with the proliferative potential of tumor cells. Our work describes a molecular mechanism that promotes this shortening of messenger RNAs in prostate cancer”, explains in a note Claudio Sette, professor of human anatomy at the Faculty of Medicine and Surgery of the Catholic University, coordinator of the research together with Pamela Bielli, associate of Human Anatomy at the Faculty of Medicine of the University of Tor Vergata. The study was conducted by Marco Pieraccioli, Department of Neurosciences of the Catholic University, Fondazione Policlinico Universitario Agostino Gemelli Irccs.

“Since a class of drugs called antisense oligonucleotides – genetic patches that adhere to messenger RNAs and defuse them – is already in clinical use against some diseases – we hypothesize that the development of specific antisense oligonucleotides could defuse this molecular mechanism”, explains Sette .

The use of messenger RNAs is determined by regulatory regions in the terminal part of the filament: these regions are recognized by proteins that promote their function. The cutting and termination of RNA can occur at different points in the regulatory region, and this process, called alternative polyadenylation, determines the length of RNA and is regulated by these proteins.

“We discovered – continues Sette – that Sam68 and XRN2 bind and repress the most distal polyadenylation sites, thus favoring the production of shorter and more efficient RNA. The perspective – he concludes – is to develop tools to block the activity of these proteins of binding to RNA and therefore deactivating this oncogenic molecular mechanism. In fact, antisense oligonucleotides are now in clinical use, for example in therapy for Spinal Muscular Atrophy, so this approach is feasible. Of course, the road in this direction is still long ”.