Studies on IQ (Institute of Chemistry) by USP have identified genes associated with an increase in pancreatic cancer tumors that are highly resistant to treatment. With the help of computer technology, scientists have been able to confirm the possible functions of genes in laboratory experiments, such as the growth and migration of tumor cells.
The results will help identify new goals for cancer therapy, as well as markers of residual or recurrent disease in treated patients. The results of the study are presented in an article published in a scientific journal Cell oncology last May 14th.
“Pancreatic cancer is the seventh leading cause of cancer death in Brazil and the world, and one of the leading causes of death: less than 5% of patients die five years after diagnosis. Currently, the only curative treatment is surgical removal. Early stages of the disease.” Professor Eduardo Moraes, who coordinated the study, told Rego Reyes Jornal da USP. “However, it is difficult to diagnose early because there are no symptoms, and when it is detected, it has spread to other parts of the body. It is still a cancer that is resistant to chemotherapy and immunotherapy.”
The study focused on the identification of long-encoded RNAs (IncRNAs) and focused on creating a high-resolution catalog of active genes in pancreatic tumors. “The functions of incRNAs are still poorly understood by scientists, for example, unlike the messenger RNAs responsible for the synthesis of proteins that reflect the genetic information contained in DNA,” the professor explains.
“We have identified lncRNA genes that play an oncogenic role, in other words, they help to show characteristics such as high proliferation, substrate-independent growth, migration and invasion associated with tumor cell damage,” the professor explains.
The study analyzed a set of expressed genes (transcript) of 14 pancreatic tumors and non-tumor pancreatic tissue from patient samples.
“For this, all the RNA was isolated, and then libraries were prepared for high-capacity sequencing,” Reiss said. “Sequencing data were bioinformatically analyzed to restore the RNA sequence reflected in the pancreas and to identify aberrant expressive lncRNAs in tumors relative to normal tissues.”
Functions
“From high-resolution sequencing of active RNA in tumors and normal pancreatic tissue, we identified” signatures “of lncRNAs that create aberrant expressions in tumors, hundreds of which have not been described in the literature. professor.
“Functional analysis of the collection of lncRNAs in the lines of pancreatic tumor cells confirmed that the silence of these RNAs confirmed that they were oncogenic lncRNAs and reduced tumor characteristics such as proliferation, migration, and invasion.”
Using a computational method based on co-expression networks of genes, the study assigned a role to several oncogenic lncRNAs and demonstrated biological processes in which they acted and could be confirmed experimentally. “We confirmed this method by showing that one of these RNAs, lncRNA, is needed to repair DNA in tumor cells exposed to UCA1 ionizing radiation,” Rice said.
The study will now continue to investigate the effects of individual and combined mutations oncogenic lncRNAs described in the study, using in vivo tumor models.
“To do this, we use a collection of xenotumors that we have in our laboratory, taken from patients with pancreatic tumors and implanted in immunosuppressed mice,” said the professor. “We also intend to assess the presence of lncRNAs in the exosomes, vesicles, and biological fluids of patients with pancreatic cancer during treatment.”
“These experiments will be important to assess the potential of lncRNAs as a therapeutic target or as markers for the detection of recurrent or recurrent disease in patients treated for pancreatic cancer,” Reis said. “Thus, in addition to improving knowledge of RNA biology, the work contributes to new molecular diagnostic goals and possible therapeutic interventions to control disease.”
The study was conducted in collaboration with a multidisciplinary team from the Department of IQ Biochemistry, biochemists, molecular and cell biologists, bioinformatics specialists, and physicians from various USP departments. FAPESP (São Paulo State Research Support Foundation).
The clinical samples analyzed in the study were obtained from the biobank of the AC Camargo Oncology Center in São Paulo, which also contributed to the work of the doctors of this institution.