Scientists looking at the genetic code of leukaemia cells believe they have found a possible new therapeutic approach targeting ‘noncoding RNAs’.
These molecules are produced through gene transcription, and are not translated into proteins but have regulatory functions such as cell growth and cell division.
Now, a German research team have found a noncoding RNAs which could be a potential weakness in acute myeloid leukaemia (AML) cells.
The team, led by Dr Jan-Henning Klusmann and Prof Dirk Heckl from Goethe University in Frankfurt, focused on non-coding RNAs, because cancer cells typically show a massive disruption of regulatory processes. They made an inventory of these molecules in AML cells to compare the differences to healthy blood stem cells.
From this they found that the cancer cells expressed nearly 500 noncoding RNAs differently to healthy cells.
To identify the most important molecules, the team ‘turned off’ these RNA molecules one by one. In doing this, they found one they called MYNRL15, which when switched off meant the cancer cells were no longer able to replicate.
Disruption of two specific regions of MYNRL15 altered the 3D structure of the nearby genome, which supressed leukaemia cell growth.
This effect was seen in several different acute myeloid leukaemia cell lines, from children and adult patients, the team explain in the journal iScience recently.
Dr Klusmann said: “In our study, we systematically examined noncoding RNAs and their genes in acute myeloid leukaemia cells for the first time, and in the process we identified a gene locus that constitutes a promising target for developing a therapy in the future.
“The regulatory function we observed is due to the MYNRL15 gene itself. This led to the deactivation of genes that acute myeloid leukaemia cells need for survival.
“The fact that all the leukemias we studied were dependent on this gene locus tells us it must be important.”
Next, the team plan to develop a new therapy specifically targeting cancer cells’ dependence on MYNRL15.
Source:
Ng M, Verboon L, Issa H, Bhayadia R, Vermunt MW, Winkler R, Schüler L, Alejo O, Schuschel K, Regenyi E, Borchert D, Heuser M, Reinhardt D, Yaspo ML, Heckl D, Klusmann JH. (2023) “Myeloid leukemia vulnerabilities embedded in long noncoding RNA locus MYNRL15.” iScience, doi: 10.1016/j.isci.2023.107844
Link: https://www.cell.com/iscience/fulltext/S2589-0042(23)01921-1
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