At the USP Institute of Chemistry (IQ), studies have identified genes associated with the growth of highly resistant pancreatic cancer tumors. Through computational technology, scientists could also assign possible functions, such as tumor cell growth and migration, to genes and confirm them in laboratory experiments.
The results of the study will help define new targets for cancer treatment, as well as markers of residual or recurrent disease in treated patients. The conclusions of this study are presented in articles published in scientific journals. Cellular oncology May 14, last year.
“Pancreatic cancer is the seventh leading cause of cancer death in Brazil and the world and is one of the most deadly. Patients with a survival rate of less than 5% 5 years after diagnosis are currently the only one. Curative treatment is early surgical resection. The stage of the disease, “reports Eduardo Moraes Lego Reis, who coordinated the study, to the Journalda USP. “But early diagnosis is difficult due to the absence of symptoms, and when it is detected, it often has already spread to other parts of the body. It is still resistant to chemotherapy and immunotherapy. I have cancer. “
This study focuses on the identification of long non-coding RNAs (IncRNAs) and aims to create a high-resolution catalog of active genes for pancreatic tumors. “For example, unlike messenger RNA, which is involved in the synthesis of proteins that express the genetic information contained in DNA, the function of IncRNA is not yet well understood by scientists,” explains the professor.
“We have identified a lncRNA gene that plays a carcinogenic role, which means it contributes to tumor cells that exhibit features associated with malignant tumors, such as high growth, substrate-independent growth, migration, and invasion,” he said. Explains.
In this study, we analyzed a series of genes (transcriptomes) expressed in 14 pancreatic tumors and non-neoplastic pancreatic tissue from samples taken from patients.
“For this, all RNA was isolated, followed by a library for high-volume sequencing,” explains Reis. “The data from sequencing was subjected to bioinformatics analysis to reorder the RNA expressed in the pancreas and identify lncRNAs that show aberrant expression in tumors compared to normal tissue. . “
function
“High-resolution sequencing of active RNA in tumors and normal pancreatic tissue has identified the” signature “of lncRNAs that produce aberrant expression in tumors. Hundreds of them have not been published and are not mentioned in the literature. Some of them correlate with patient survival. .. And the value for creating a prognosis for illness in the clinic, “says the professor.
“Functional analysis of a series of lncRNAs in pancreatic tumor cell lines has shown that silencing of these RNAs reduces tumor properties such as proliferation, migration, and infiltration, confirming that they are carcinogenic lncRNAs. “
Using a computational approach based on gene co-expression networks, studies have assigned roles to several carcinogenic lncRNAs and have shown biological processes in which they act and may be experimentally confirmed. “We validated this approach by showing that one of these RNAs, lncRNAUCA1, is required for DNA repair in tumor cells exposed to ionizing radiation,” Reis said.
The study continues to investigate the effects of individual and combined silencing of carcinogenic lncRNAs described in the study, currently using an in vivo tumor model.
“For this, we use a collection of heterologous tumors already available in our laboratory, generated from pancreatic tumors removed from patients and transplanted into immunosuppressed mice.” The professor points out. “We will also assess the presence of lncRNA in exosomes, vesicles secreted by tumor cells, and body fluids of patients with pancreatic cancer being treated.”
“These experiments are important to assess the potential of lncRNA as a therapeutic target or as a marker for the detection of residual or recurrent disease in patients with pancreatic cancer being treated,” Reis emphasizes. increase. “Thus, in addition to advancing knowledge about the biology of these RNAs, this study also contributes to new molecular targets for diagnosis and possible therapeutic interventions to control the disease. increase.”
The study was conducted in IQ’s biochemistry department with the help of an interdisciplinary team of biochemists, molecular biologists, cell biologists, bioinformatics experts, and doctors from various departments of the USP. FAPESP (Research Support Foundation of the State of São Paulo).
The clinical samples analyzed in this study were obtained from the biobank of the AC Camargo Cancer Center in São Paulo and also contributed to the work of the institution’s physicians.