They detect a modification in the RNA that could be key in breast cancer

Cancer is a disease that depends on many factors and, in addition, there are many types of cancers. It is important to identify the risk factors for cancer: for this, population groups are analyzed and the characteristics of those who suffer from cancer are compared with those of those who do not; in this way, it is seen if the people who suffer from it have a greater or lesser probability of having a certain characteristic.

The BIOMICs research team at the University of the Basque Country (UPV/EHU) has analyzed one of the most frequent changes that occurs in messenger RNA: methylation (addition of a group made up of one carbon and three hydrogens, in a position determined from the RNA molecule). A certain type of methylation results in N6-methyladenosine (m⁶A). Numerous studies have shown that the m⁶A participates in the regulation of most of the processes of RNA metabolism. But the impact of this change on the regulation of gene expression, its function in cellular processes and its possible influence on the development and progression of diseases such as breast cancer has been unknown.

The BIOMICs research team has measured the amount of m⁶A present in breast cancer in order to find new therapeutic targets in the future. “Methylations of m⁶A are very common, as they are produced to regulate RNA function. But in cancer this regulation is lost, and we wanted to observe the role that RNA methylation plays in this disorder”, says Felix Olasagasti, a researcher in the BIOMICs group.

From left to right, Felix Olasagasti, Daniel Azkarate and Marian Martinez de Pancorbo, members of the BIOMICs group. Missing from the photograph is Tamara Kleinbielen, who has done most of this research work. (Photo: Nuria González, UPV/EHU)

The results show that “the global percentage of RNA methylation in tumor tissues is lower than in healthy tissues, and the difference is significant,” says the doctor in biochemistry and molecular biology. Furthermore, this is the first study to describe the methylation profile of m⁶A in the different subtypes of breast cancer: “We have seen that the difference detected in the methylation of cancer cells appears with a different profile depending on each type of breast cancer. Breast cancers are classified according to certain characteristics. We have seen that, in addition to the characteristics used for said classification, there are also differences in RNA methylation in the different cancer subtypes”.

The researcher stresses the importance of this finding: “The better we know what each subtype of cancer is like or how we should characterize it, the more likely we are to obtain a treatment to combat it.” In any case, the researcher points out that there is still a long way to go. “From this study it can be deduced that the alteration of methylation could affect the proteins derived from these RNAs, which could ultimately affect the cancerous nature of the cell.” That is the hypothesis that researchers handle.

In the study they have used a massive sequencing technique. “We have collected a lot of data. We need to analyze them in more detail to see in which genes the changes occur. Once the genes are well determined, the next step would be to observe to what extent that affects the proteins and then see what effect that may have. Seeing that the percentage of methylation is lower in cancer cells, we could think that increasing this percentage could help regenerate these cells”. According to Olasagasti, each of these steps would constitute a research project.

The study is titled “In silico identification and in vitro expression analysis of breast cancer-related m⁶A-SNPs”. And it has been published in the academic journal Epigenetics. (Source: UPV/EHU)