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.
Highlights
MYC is a transcription factor regulating global gene expression through heterodimerization with the protein myc-associated factor X (MAX) [1,2,3]
By profiling long noncoding RNAs (lncRNAs) expression in colorectal cancer (CRC), we found that about 7% of lncRNAs are dysregulated in CRC and that 1060 lncRNAs are downregulated in CRC (Figure 1a) [13]
Because MYC is overexpressed in the CRC cells and tissues used in the previous study, a part of the lncRNAs could be repressed by MYC
Summary
MYC is a transcription factor regulating global gene expression through heterodimerization with the protein myc-associated factor X (MAX) [1,2,3]. Through the genome-wide regulation of gene expression, MYC is involved in diverse cellular processes including cell growth, cell cycle, apoptosis, angiogenesis, cell differentiation and genomic instability [4]. MYC is primarily overexpressed and/or amplified in numerous types of cancer through various mechanisms such as retroviral transduction and MYC translocation [4, 5, 8]. Posttranscriptional regulation of MYC contributes on the overexpression of MYC in cancer. The stability of MYC protein modulated by phosphorylation is regulated by promyelocytic leukemia zinc finger (PLZF) protein and long noncoding RNA PVT1 [9, 10]
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