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Because liver cancer has many types, strong inheritance, and easy recurrence, identifying biomarkers that can predict disease progression is a key goal in fighting the disease. Recently, researchers have developed a method to identify the most common form of liver cancer — hepatocellular carcinoma (HCC) — based on splicing biomarkers, and believe this method can also be applied to other types of cancer.
Splicing refers to a process in which RNA information copied from a gene is edited before it can be used to make a specific protein. A gene can produce multiple RNA messages, and each message produces a different protein variant or "isoform." Many diseases are related to errors or variations in RNA splicing, which can result in proteins with different or abnormal functions. Recent research has identified splicing irregularities in liver cancer cells, and Krainer's team developed a method that can comprehensively analyze all RNA information produced by a given gene, testing their approach by analyzing RNA from HCC cells collected from hundreds of patients.
The researchers found that a specific splicing isoform of the AFMID gene is associated with low patient survival. These variants result in cells making truncated versions of the AFMID protein, which are associated with mutations in the TP53 and ARID1A tumor suppressor genes in adult liver cancer cells.
The researchers hypothesized that these mutations are related to low levels of a molecule called NAD+, which is involved in repairing damaged DNA. Repairing AFMID splicing may lead to increased production of NAD+ and improved DNA repair capacity. If achievable, AFMID splicing could become both a therapeutic target and a source of new drugs for liver cancer. Preliminary experiments show the team's research is on the right track, and further data results are expected to bring meaningful benefits to liver cancer patients in the future
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About Sai Sree
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