title: C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia.
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.
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.
authors.forename: Ze-Chuan
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Luo
authors.affiliation: Union Clinical Medical College, Fujian Medical University, Fuzhou, P.R. China.|Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, P.R. China.
authors.forename: Shao-Yuan
authors.initials: SY
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C489427:MYC protein, human; D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C487931:mirnlet7 microRNA, human; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin
keywords: APL; Let-7; Myc; PML/RARα; ceRNA