Posttranscriptional regulation of PTEN dosage by noncoding RNAs.
The classic "two-hit" model of tumor-suppressor inactivation, originally established by mathematical modeling of cancer incidence, implies that tumorigenesis requires complete loss of function of tumor-suppressor genes. Although this is true in some tumor types, the exact nature of tumor-suppressor deregulation varies depending on tissue type, stage of cancer development, nature of coexisting molecular lesions, and environmental factors. Emerging evidence has indicated the functional importance of PTEN (phosphatase and tensin homolog) dosage during tumor development. Among the key regulators of PTEN dosage are a number of noncoding RNAs, including microRNAs (miRNAs) and pseudogenes, which regulate PTEN abundance at the posttranscriptional level. Various studies have revealed the essential roles of these PTEN-targeting noncoding RNAs during tumor development, thus providing a paradigm to explore the molecular mechanisms underlying the dosage-dependent effects of key oncogenes and tumor suppressors.
Division of Cellular and Developmental Biology, Molecular and Cellular Biology Department, University of California at Berkeley, Berkeley, CA 94705, USA. lhe@berkeley.edu
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D000818:Animals; D002471:Cell Transformation, Neoplastic; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D034622:RNA Interference
D035683:MicroRNAs; D051059:PTEN Phosphohydrolase