Myc/miR-378/TOB2/cyclin D1 functional module regulates oncogenic transformation.
The c-Myc transcription factor activates a cascade of downstream targets to form a complex transcriptional program that ultimately leads to cellular transformation. Although a large number of protein-encoding genes as well as non-coding RNAs were identified as Myc targets, only a few have been validated to be functionally important for c-Myc-driven transformation. Here, we identify a microRNA (miRNA), miR-378, as a novel target of the c-Myc oncoprotein that is able to cooperate with activated Ras or HER2 to promote cellular transformation. Mechanistically, miR-378 achieves this oncogenic effect, at least in part, by targeting and inhibiting the anti-proliferative BTG family member, TOB2, which is further elucidated as a candidate tumor suppressor to transcriptionally repress proto-oncogene cyclin D1. Therefore, our study identifies miR-378-TOB2-cyclin D1 as a functional module to mediate the cross talk between Myc and Ras signaling in cellular transformation.
Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore.
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Feng
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Li
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Aau
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CH
Wong
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Yang
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Yu
D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; C000715470:MAS1 protein, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C402648:TOB2 protein, human; D019938:Cyclin D1