Neat1 and SAMMSON: similar, yet different anti-cancer targets

12 November 2016

​A team of researchers led by Chris Marine (VIB-KU Leuven) has shown that NEAT1, a long non-coding RNA, plays an important role in the survival of highly dividing cells – cancer cells in particular. The research has a striking similarity to earlier findings by the Marine lab about SAMMSON, a long non-coding RNA gene on which the growth of aggressive skin cancer is highly dependent. Chris is happy to shed some light on the similarities and differences between both papers.

A large share of the human genome has long been considered ‘junk DNA’, because it doesn’t contribute to proteins. However, recent insights indicate that many non-coding RNAs play an important role in biological processes and diseases after all. NEAT1 and SAMMSON are prime examples.

Chris, in what way are the NEAT1 and SAMMSON papers similar?
Chris: “The two projects each identified a long non-coding RNA as a potential anticancer therapeutic target. NEAT1 and SAMMSON are also both ‘ trans-acting’, which means that they function away from the locus they originate from. In both cases, we identified the proteins that control their expression: p53 in the case of NEAT1, SOX10 in the case of SAMMSON.

Importantly, both are cancer- cell specific therapeutic targets: they are required for the growth
or even the survival of cancer cells, but they are dispensable for normal cell function. This means NEAT1 and SAMMSON can both be safely targeted in vivo, using an antisense-based therapeutic approach, which is clinically-compatible. And lastly, both RNA molecules have a clear potential as
biomarkers, either of melanoma malignancy (SAMMSON) or as a predictive marker of response to
chemotherapy (NEAT1).”

There are some remarkable differences as well.
Chris: “Yes. First of all, SAMMSON is a melanomaspecific RNA molecule, whereas NEAT1 is not restricted to one specific cancer type. Secondly, SAMMSON functions by modulating the biology of
mitochondria, which provide energy to the cancer cells. NEAT1, on the other hand, contributes to the assembly of ‘paraspeckles’, subnuclear particles in the cell nuclei of cancer cells that prevent
accumulation of DNA damage. All told, our data highlight that lncRNAs are capable of transacting a wide repertoire of regulatory functions.”

SAMMSON paper: Leucci et al., Nature 2016
NEAT1 paper: Adriaens et al., Nature Medicine 2016

Chris Marine (VIB-KU Leuven)
©VIB-Ine Dehandschutter