MicroRNA-34 Genes Cooperate with p53 to Suppress Prostate Cancer

Cornell researchers report they have discovered direct genetic evidence that a family of genes, called microRNA-34 (miR-34), are bona fide tumor suppressors. The study was published online in the journal Cell Reports on March 13, 2014. Previous research at Cornell and elsewhere has shown that another gene, called p53, acts to positively regulate miR-34. Mutations of p53 have been implicated in half of all cancers. Interestingly, miR-34 is also frequently silenced by mechanisms other than p53 in many cancers, including those with p53 mutations. The researchers showed in mice how interplay between genes p53 and miR-34 jointly inhibits another cancer-causing gene called MET. In absence of p53 and miR-34, MET overexpresses a receptor protein and promotes unregulated cell growth and metastasis. This is the first time this mechanism has been proven in a mouse model, said Dr. Alexander Nikitin, a professor of pathology in Cornell’s Department of Biomedical Sciences and the paper’s senior author. Chieh-Yang Cheng, a graduate student in Dr. Nikitin’s lab, is the paper’s first author. In a 2011 Proceedings of the National Academy of Sciences paper, Dr. Nikitin and colleagues showed that p53 and miR-34 jointly regulate MET in cell culture but it remained unknown if the same mechanism works in a mouse model of cancer (a special strain of mice used to study human disease). The findings suggest that drug therapies that target and suppress MET could be especially successful in cancers where both p53 and miR-34 are deficient. The researchers used mice bred to develop prostate cancer, then inactivated the p53 gene by itself, or miR-34 by itself, or both together, but only in epithelium tissue of the prostate, as global silencing of these genes may have produced misleading results.
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