2023-05-16 16:00:06
Scientists from the Josep Carreras Leukemia Research Institute (IJC), led by Manel Esteller, have discovered a key epigenetic alteration to anticipate the clinical course of liver cancer. It is about the deactivation of the NSUN7 gene, in turn an epigenetic editor of RNA. Tumors with this alteration usually have a poor clinical prognosis, although research indicates that they would be more vulnerable to bromodomain inhibitors, a family of anticancer drugs. The results of the study have been published in Molecular Cancer
Liver cancer is a very common type of tumor. In fact, in many countries it is among the three most commonly detected. Every year around a million cases are diagnosed worldwide. In addition, it is a type of tumor that is highly aggressive, with a mortality close to 80% of patients.
Esteller’s group, director of the IJC, ICREA Research Professor and Professor of Genetics at the University of Barcelona, has experience in the study of liver cancer, as he was the first to determine the epigenome of this tumor and thus identify the Major chemical alterations to DNA that change its gene expression.
Manel Esteller’s group was the first to determine the epigenome of liver cancer
In the investigation, signed by Vanessa Ortiz-Barahona y Martha Soler As main authors, the scientific team has focused on the study of chemical modifications to RNA, the intermediary molecule between genetic information and proteins, the true tools of the cell.
In this sense, Esteller highlights that “in the last five years, we have contributed to demonstrating that not only the chemical regulation of DNA is altered in cancer but also the ‘marks’ that control RNA activity”. The IJC determined for the first time the epigenome of this tumor, which made it possible to identify the main chemical alterations of DNA that change its genetic expression.
During the study of who controls these chemical modifications of the RNA (the so-called epitranscriptoma), the researchers found that the genNSUN7 it was clearly altered in liver cancer.
worst survival
“We observed that the NSUN7 gene suffered a loss of functionality in liver tumors and this caused a degradation of their RNA targets, finally leading to a superactivation of the MYC oncogene”, points out Esteller.
Determining the epigenetic situation of NSUN7 could have high clinical value and help design a more precise and personalized therapy in liver cancer patients.
Activation of oncogenes is usually associated with worst survival, as the results of the study pointed out. However, Esteller comments that “at the same time we verified that the mentioned tumors were more sensitive to drugs that blocked MYC, as the so-called bromodomain inhibitors”. This opens a new therapeutic avenue that is worth exploring in liver cancer clinical trials based on the activation status of NSUN7.
An unintended consequence of the research is that those liver tumors with intact NSUN7 could be more receptive to immunotherapy. In this way, determining the epigenetic situation of NSUN7 in liver cancer patients could have high clinical value and help to design a more precise and personalized therapy for the patient.
Reference:
Soler, M. et al. “Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer” Molecular Cancer (2023)
Rights: Creative Commons.
#Epigenetic #weaknesses #liver #cancer #discovered #improve #treatment