Oncotarget

Research Papers:

C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia

Ye Ding, Ze-chuan Wang, Yi Zheng, Zheng Hu, Yang Li, Dong-feng Luo and Shao-yuan Wang _

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Oncotarget. 2016; 7:56422-56430. https://doi.org/10.18632/oncotarget.10896

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Abstract

Ye Ding1, Ze-chuan Wang1, Yi Zheng1, Zheng Hu1, Yang Li2, Dong-feng Luo1, Shao-yuan Wang1,2

1Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China

2Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, P.R. China

Correspondence to:

Shao-yuan Wang, email: shaoyuanwang@mail.fjmu.edu.cn

Keywords: ceRNA, APL, Let-7, Myc, PML/RARα

Received: March 10, 2016     Accepted: July 09, 2016     Published: July 28, 2016

ABSTRACT

Recent reports have described a new post-transcriptional regulation that RNA transcripts can crosstalk with each other by competing for their common microRNAs. These RNA transcripts termed competing endogenous RNAs (ceRNAs) regulate the distribution of miRNAs on their targets. One corollary from ceRNA interaction is that chromosomal translocation in acute promyelocytic leukemia (APL) would perturb ceRNA regulation due to altered expression of 3’UTRs. In our study, we demonstrate that expression of PML/RARα, the APL-associated fusion oncogene is repressed by c-Myc mRNA transcript independent of protein-coding function but dependent upon microRNA. Attenuation of c-Myc transcript results in PML/RARα-degraded cellular phenotypes in APL cells, but these Myc reduction-associated cell phenotypes are sufficient to abrogate in a microRNA dependent manner. We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARα through altering miRNA targets. These results indicate that c-Myc mRNA represses PML/RARα expression via altering the distribution of let-7 miRNAs on their targets. Our findings reveal a previously unrecognized role of c-Myc as a potential ceRNA for PML/RARα in APL.


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