PNAs: computer technology helps to reveal the molecular mechanism of cancer deterioration

February 19, 2020 / BIOON / -- recently, a study led by children's Hospital of Philadelphia (CHOP) revealed the relationship between variable protein cleavage and oncogene The results were published in PNAS "Our research provides insights into the relationship between cancer driven genes and alternative splicing, and these findings can be used to guide the development of cancer therapies targeting alternative splicing," said Dr Xing, director of the center for computing and genomics Selective splicing is an essential molecular process in cells, which allows genes to encode different protein products according to the different positions of RNA cutting or splicing before transforming RNA into protein Cancer cells often use this process to produce proteins that promote growth and survival, allowing them to replicate and metastasize uncontrolled This happens in many cancers, including prostate cancer However, scientists do not fully understand the process leading to this change (image source: www Pixabay Com) to better understand the causes and consequences of variable splicing changes in cancer progression, the team studied RNA sequences in nearly 900 prostate tissue samples, including healthy prostate tissue and local or aggressive metastatic tumor tissue To effectively analyze such a large data set, the team created a new calculator called rmats turbo Using the procedure, the researchers identified more than 13000 variable splicing events in the 900 prostate samples Next, the team developed an analytical tool called pegasas (alternative splicing pathway enrichment guide activity study) to identify potential cancer driving genes and pathways associated with these alternative splicing changes They found that Myc, a gene involved in normal cell function, has been amplified in many cancers and is associated with alternative splicing changes in genes that regulate alternative splicing Using engineered human prostate cells to turn on or off myc activity, the researchers further confirmed that these alternative splicing changes were indeed driven by Myc The researchers then applied the same pegasas strategy to breast and lung cancer samples and found the same association between myc activity and other splices, suggesting that myc activation (which leads to splicing disruption) occurs in many cancers Source of information: new computational tools identify alternative splicing changes in aggressive cancers original source: John W Phillips El Al., "pathway guided analysis identifiers myc dependent alternative pre mRNA splicing in aggressive progress cancers," PNAs (2020) Www.pnas.org/cgi/doi/10.1073/pnas.1915975117