A genetic mutation key that is made at an early stage of cancer changes the RNA “dark matter” and causes the release of unknown RNA biomarkers so far for the early detection of canceraccording to a new study by researchers at the University of California (UC Santa Cruz), in United States of Americapublished in the journal Cell Reports.
researcher studied the effects of mutations in the KRAS genewhat lies in between the most frequently mutated genes in all types of cancer, including pancreatic, lung and colon cancer.
KRAS is believed to be a “driver” mutation initially leads to cancer formationmaking it essential to understand and recognize cancer in its earliest stages.
In this study, the lab of Assistant Professor of Biomolecular Engineering Daniel Kim focused on determining KRAS mutations in lung cancer its effects on RNA “dark matter”generated from 75% of the 3,000 million base pairs of the human genome with the goal of discovering new RNA biomarkers for early detection of cancer.
“The sooner this is discovered someone has cancerthe more likely you are to survive treatment and surgery,” says Kim, who is affiliated with the UC Santa Cruz Genomics Institute, the Institute for Stem Cell Biology and the Center for RNA Molecular Biology and is an associate member of the Stanford Canary Center for Cancer Screening.
“Millions of people die from cancer every day worldwide, and there is an urgent need to develop highly sensitive and specific diagnostic tests that enable early detection of cancer before it has spread to other parts of the body,” he adds.
Kim’s lab studies how the KRAS gene regulates the transcriptome, which is all RNA produced in a cell. That The most well-known function of RNA is that of “messenger”. that takes the genetic information encoded in DNA and turns it into protein, but recent advances in genomics have shown this to be the case The vast majority of RNA is non-coding and does not make proteins..
Kim focuses on Investigation of this non-coding RNAWith the goal of using this information to better understand cancer development and to identify new biomarkers for early detection from the same.
In this study, led by Roman Regiardo, a PhD student in Biomolecular Engineering in Kim’s lab and an F99/K00 fellow at the institutes US National Healththe researchers found that KRAS mutations in lung cancer also activate genes that are stimulated by interferon, which can be seen in many types of cancer, the cause of which is unclear.
They also found that mutations in KRAS cause silencing of a class of genes called KRAB zinc finger genes, something Kim said hadn’t been seen before context cancer. When these genes are turned off, certain types of non-coding RNAs are abnormally activated.
Many of these newly activated noncoding RNAs originate from transposable elements, which are repeating elements that occur in the millions throughout the human genome, some of which are that have the potential to jump around and alter the genome.
The researchers discovered that these transposable element RNAs are not only activated within the mutated KRAS cells, but are also transported out of the cells. Since it is known that RNAs are released into the bloodstream by cancer cells, these transposable element RNAs could act as a signal to the cancer-causing mutant KRAS detectable in the blood by RNA sequencing.
Kim believes that this signing of strong RNA and Robusta shows promise for diagnosing cancer in its earliest stages. This could be done using a blood test known as a liquid biopsy, a minimally invasive approach compared to a traditional biopsy of tumor tissue.
These newly published results were obtained using cell culture models into which the researchers introduced the mutant KRAS non-cancerous lung cellsdriving them into a cancerous state.
They performed RNA sequencing using different techniques and performed computational analysis to determine which RNA is most abundant in cells expressing the mutant KRAS. versus control cells.
The researchers performed additional epigenomic profiling experiments, who observe how genes are turned on or off without changing the DNA sequence itself. They also performed extracellular vesicle isolations and identified which RNA is packaged in extracellular vesicles and preferentially secreted by mutant KRAS-affected cancer cells.
In ongoing and future work, Kim’s lab aims to further confirm his novel findings by analyzing blood samples from lung cancer patients to validate that their newly released RNA signatures identified are present in these patients.
Furthermore, they envision that the methods developed in this study could be used as Framework for the development of a biopsy platform RNA liquid for early detection of various types of cancer.
“Now that we know the RNA signatures of it event so early in cancer, This will help us to develop new methods for early detection of cancer, which we hope will help save many lives people in the futureemphasizes Kim.