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 valid...

Full description

Saved in:

Bibliographic Details
Published in:	Oncogene Vol. 30; no. 19; pp. 2242 - 2251
Main Authors:	Feng, M, Li, Z, Aau, M, Wong, C H, Yang, X, Yu, Q
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 12-05-2011 Nature Publishing Group
Subjects:	631/337/384/331 631/80/86 692/420/755 Apoptosis Base Sequence Biological and medical sciences c-Myc protein Cell Biology Cell Cycle Proteins - physiology Cell Line, Tumor Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic Cyclin D1 Cyclin D1 - physiology Cyclin-dependent kinases ErbB-2 protein Fundamental and applied biological sciences. Psychology Gene Knockdown Techniques Genetic transformation Human Genetics Humans Internal Medicine Medicine Medicine & Public Health MicroRNAs MicroRNAs - physiology miRNA Molecular and cellular biology Myc protein Oncology original-article Proteins Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - physiology Ras protein Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering Tumor suppressor genes Tumors miR-378 cyclin D1 TOB2 Myc Gene silencing Regulation(control) RNA interference Micro RNA Cyclin D1 Onc gene Carcinogenesis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0950-9232 1476-5594
DOI:	10.1038/onc.2010.602