Sonia Guil, from the Josep Carreras Leukemia Research Institute, and Lourdes Farré, from the Bellvitge Biomedical Research Institute (Idibell), have described how in a region of the non-coding genome there is an intermediate molecule involved in the regulation of key processes for the development and differentiation of cells, and for the tumor cell expansion.
The work, published in Nature Communications, reveals how the RNA RPSAP52 molecule It triggers the proliferation of cells and cancels their differentiation, making it easier for tumor cells to multiply and spread.
Non-coding regions of the genome are DNA sequences that do not encode a protein and, therefore, do not consider conventional genes. Normally, when the DNA of a region that does encode a gene is processed, a machinery that reads the DNA is started, transcribes it to another simpler RNA molecule and this transcription is translated into a protein with a specific function.
On the contrary, some regions that do not code for any protein can be read and transcribed, although in the end they are not translated, generating intermediate molecules whose function is worth studying because they can be key in the regulation and signaling of cellular processes. This is the case of this study.
Guil and his team have analyzed a non-coding sequence that is linked to another sequence that does code for a common oncogene in different types of cancer, called HMGA2. The non-coding sequence that originates RPSAP52, it is just ‘ahead’ of HMGA2, and it has been found that it regulates the chain of events responsible for tumor cells increasing in number and cancerous tissues expanding.
“RPSAP52 regulates the entire signaling path HMGA2 / IGF2BP2 / RAS. Its activation promotes growth and keeps cells in the state of undifferentiation so typical of the most aggressive tumor cells, ”explains Guil.
“Under normal conditions, in healthy RPSAP52 cells it is only expressed at the embryonic level and is silenced in most adult tissues. In a large number of cancers, however, it is once again expressed aberrantly and promotes the pluripotent character and high replication of the cells, ”adds the researcher.
The study has been carried out combining in vitro approaches with in vivo studies in animal models, and the RPSAP52 tumorigenic role in breast tumors and sarcoma, in which it can even have a predictive value as a biomarker.
For Guil, the fact that this non-coding RNA is re-expressed in most human tumors and has a relevant role reinforces the function of the non-coding genome, often underestimated in the regulation of cellular programs and especially in the pathological context.
“From the point of view of translational research, the findings are significant because these types of molecules are often present at low levels and, therefore, can be attacked and eradicated more easily than the coding genes,” defends the expert.
The next steps will focus on generating tumor models in vivo in which the administration of small molecules that destroy RPSAP52 can be tested, to study its effect on tumor growth.