MYC-repressed long noncoding RNAs antagonize MYC-induced cell proliferation and cell cycle progression

// Taewan Kim 1, * , Ri Cui 2, * , Young-Jun Jeon 2 , Paolo Fadda 2 , Hansjuerg Alder 2 , Carlo M. Croce 2 1 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA * These authors have contributed equally to this work Correspondence to: Carlo M. Croce, e-mail: carlo.croce@osumc.edu Keywords: MYC, long noncoding RNA, cell proliferation, cell cycle Received: April 09, 2015      Accepted: April 28, 2015      Published: May 11, 2015 ABSTRACT The transcription factor MYC is a proto-oncogene regulating cell proliferation, cell cycle, apoptosis and metabolism. The recent identification of MYC-regulated long noncoding RNAs (lncRNAs) expands our knowledge of the role of lncRNAs in MYC functions. Here, we identify MYC-repressed lncRNAs named MYCLo-4, -5 and -6 by comparing 3 categories of lncRNAs (downregulated in highly MYC-expressing colorectal cancer, up-regulated by MYC knockdown in HCT116, upregulated by MYC knockdown in RKO). The MYC-repressed MYCLos are implicated in MYC-modulated cell proliferation through cell cycle regulation. By screening cell cycle-related genes regulated by MYC and the MYC-repressed MYCLos, we identified the MYC-repressed gene GADD45A as a target gene of the MYC-repressed MYCLos such as MYCLo-4 and MYCLo-6.