PMID- 28560387
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20211204
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 1
DP  - 2017 Jul
TI  - Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the 
      neuronal-specific RNA-binding protein HuD.
PG  - 545-550
LID - 10.3892/or.2017.5664 [doi]
AB  - Neuroblastoma is a childhood cancer originating from embryonic neural crest 
      cells. Amplification of the proto‑oncogene N-myc, seen in ~30% of neuroblastoma 
      tumors, is a marker for poor prognosis. Recently discovered small regulatory 
      RNAs, microRNAs (miRNAs), are implicated in cancers, including neuroblastoma. 
      miRNAs downregulate the expression of genes by binding to the 3'-untranslated 
      regions (3'-UTRs), thereby inhibiting translation or inducing degradation of 
      cognate mRNAs. Our study sought to identify miRNAs that regulate N-myc expression 
      and thereby malignancy in neuroblastoma. miRNAs whose expression negatively 
      correlates with N-myc expression were identified from a miRNA microarray of 
      4 N-myc-amplified neuroblastoma cell lines. Three of these miRNAs (miR-17, 
      miR-20a and miR-18a) belong to the miR-17-92 cluster, previously shown to be 
      upregulated by N-myc. qPCR validation of these miRNAs in a larger panel of cell 
      lines revealed that levels of miR-17 were inversely proportional to N-myc mRNA 
      amounts in the N-myc-amplified cell lines. Notably, miR-17 also downregulated 
      N-myc protein synthesis in the N-myc-amplified cells, thereby generating a 
      negative feedback regulatory loop between the proto-oncogene and this miRNA. 
      Moreover, the neuronal-specific RNA-binding protein HuD (ELAVL4), which regulates 
      the processing/stability of N-myc mRNA, competes with miR-17 for a binding site 
      in the 3'-UTR of N-myc. Thus, N-myc levels appear to be modulated by the 
      antagonistic interactions of both miR-17, as a negative regulator, and HuD, as a 
      positive regulator, providing further evidence of the complex cellular control 
      mechanisms of this oncogene in N-myc-amplified neuroblastoma cells.
FAU - Samaraweera, Leleesha
AU  - Samaraweera L
AD  - Department of Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, 
      USA.
FAU - Spengler, Barbara A
AU  - Spengler BA
AD  - Department of Biological Sciences, Fordham University, Bronx, NY 10458, USA.
FAU - Ross, Robert A
AU  - Ross RA
AD  - Department of Biological Sciences, Fordham University, Bronx, NY 10458, USA.
LA  - eng
GR  - R01 CA077593/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170524
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (3' Untranslated Regions)
RN  - 0 (ELAV-Like Protein 4)
RN  - 0 (ELAVL4 protein, human)
RN  - 0 (MAS1 protein, human)
RN  - 0 (MIRN17 microRNA, human)
RN  - 0 (MYCN protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Proto-Oncogene Mas)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Cell Differentiation/genetics
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - ELAV-Like Protein 4/genetics/*metabolism
MH  - Feedback, Physiological
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Microarray Analysis
MH  - N-Myc Proto-Oncogene Protein/*genetics/metabolism
MH  - Neural Stem Cells
MH  - Neuroblastoma/*genetics
MH  - Neurons/metabolism
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogenes/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC5492688
EDAT- 2017/06/01 06:00
MHDA- 2018/03/27 06:00
PMCR- 2018/07/01
CRDT- 2017/06/01 06:00
PHST- 2016/10/12 00:00 [received]
PHST- 2016/11/15 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - or-38-01-0545 [pii]
AID - 10.3892/or.2017.5664 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Jul;38(1):545-550. doi: 10.3892/or.2017.5664. Epub 2017 May 24.