PMID- 26013954
OWN - NLM
STAT- MEDLINE
DCOM- 20160505
LR  - 20220321
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 89
IP  - 2
DP  - 2015 Aug
TI  - Methyl(R217)HuR and MCM6 are inversely correlated and are prognostic markers in 
      non small cell lung carcinoma.
PG  - 189-96
LID - S0169-5002(15)00244-5 [pii]
LID - 10.1016/j.lungcan.2015.05.008 [doi]
AB  - OBJECTIVES: In non small cell lung carcinoma (NSCLC), earlier studies supported a 
      prognostic value of intra-cytoplasmic HuR expression. HuR is a RNA binding 
      protein previously shown to stimulate proliferation, but the link between HuR and 
      proliferation in NSCLC has not yet been evaluated. The first objective of this 
      study was to analyze the expression of HuR in a series of NSCLC and to correlate 
      this to two proliferation markers, Ki-67 and MCM6. As potential 
      post-transcriptional regulatory mechanisms for HuR expression, two miRNAs, miR16 
      and miR519, were also analyzed. Finally, because HuR methylation could be 
      involved in its nucleocytoplasmic shuttling, the expression of methyl(R217)HuR 
      and its relation to cancer survival were determined. MATERIALS AND METHODS: 
      Immunohistochemistry was used to evaluate the expression of HuR, methy(R217)HuR, 
      Ki-67 and MCM6 in a series of 190 NSCLCs. The level of miR16 and miR519 was 
      determined by qRT-PCR. RESULTS: Higher cytoplasmic HuR staining was found in 
      tumor vs. control paired normal lung (p<0.0001), but without correlation with 
      survival. The level of methyl(R217)HuR was correlated both significantly with 
      intra-cytoplasmic HuR staining (p<0.001), and overall survival (p=0.01). MCM6 
      correlated to a poorer overall survival (p<0.01). Both MCM6 and Ki-67 were 
      positively correlated with HuR nuclear staining (p<0.0001 and p<0.001, 
      respectively). On the contrary, MCM6 and Ki-67 correlated inversely to 
      methyl(R217)HuR (p<0.001 and p=0.01, respectively). The levels of miR16 and 
      miR519 were significantly lower in tumor tissue vs. paired normal lung 
      (p<0.0001), but only miR519 correlated inversely to HuR expression (p=0.01). 
      CONCLUSION: While overall cytoplasmic HuR level was higher in tumor tissues, we 
      found unexpectedly that methyl(R217)HuR was a marker of good prognosis. 
      Furthermore, our data suggest that HuR level could be regulated by miR519. 
      Finally, we demonstrated that Ki-67 and MCM6, both correlated with HuR, are 
      valuable markers of poor prognosis in NSCLC.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Vigouroux, Charlene
AU  - Vigouroux C
AD  - Department of Pathology, CHU Nancy, France.
FAU - Casse, Jean-Matthieu
AU  - Casse JM
AD  - Department of Pathology, CHU Nancy, France; INSERM U954, Faculty of Medicine, 
      Universite de Lorraine, Nancy, France.
FAU - Battaglia-Hsu, Shyue-Fang
AU  - Battaglia-Hsu SF
AD  - INSERM U954, Faculty of Medicine, Universite de Lorraine, Nancy, France; 
      Department of Molecular Biology and Biochemistry, CHU Nancy, France.
FAU - Brochin, Lydia
AU  - Brochin L
AD  - Department of Pathology, CHU Nancy, France.
FAU - Luc, Amandine
AU  - Luc A
AD  - INGRES, EA7298, Faculty of Medicine, Universite de Lorraine, Nancy, France.
FAU - Paris, Christophe
AU  - Paris C
AD  - INGRES, EA7298, Faculty of Medicine, Universite de Lorraine, Nancy, France; 
      Department of Occupational Diseases, CHU Nancy, France.
FAU - Lacomme, Stephanie
AU  - Lacomme S
AD  - Centre de Ressources Biologiques, BB-0033-00035, CHU Nancy, France.
FAU - Gueant, Jean-Louis
AU  - Gueant JL
AD  - INSERM U954, Faculty of Medicine, Universite de Lorraine, Nancy, France; 
      Department of Molecular Biology and Biochemistry, CHU Nancy, France.
FAU - Vignaud, Jean-Michel
AU  - Vignaud JM
AD  - Department of Pathology, CHU Nancy, France; INSERM U954, Faculty of Medicine, 
      Universite de Lorraine, Nancy, France; Centre de Ressources Biologiques, 
      BB-0033-00035, CHU Nancy, France.
FAU - Gauchotte, Guillaume
AU  - Gauchotte G
AD  - Department of Pathology, CHU Nancy, France; INSERM U954, Faculty of Medicine, 
      Universite de Lorraine, Nancy, France. Electronic address: 
      g.gauchotte@chu-nancy.fr.
LA  - eng
PT  - Journal Article
DEP - 20150516
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ELAV-Like Protein 1)
RN  - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism/*mortality/pathology
MH  - ELAV-Like Protein 1/*metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*metabolism/*mortality/pathology
MH  - Male
MH  - Methylation
MH  - Middle Aged
MH  - Minichromosome Maintenance Complex Component 6/*metabolism
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Protein Transport
OTO - NOTNLM
OT  - HuR
OT  - Ki-67
OT  - Lung cancer
OT  - MCM6
OT  - miR16
OT  - miR519
EDAT- 2015/05/28 06:00
MHDA- 2016/05/06 06:00
CRDT- 2015/05/28 06:00
PHST- 2015/03/02 00:00 [received]
PHST- 2015/05/02 00:00 [revised]
PHST- 2015/05/09 00:00 [accepted]
PHST- 2015/05/28 06:00 [entrez]
PHST- 2015/05/28 06:00 [pubmed]
PHST- 2016/05/06 06:00 [medline]
AID - S0169-5002(15)00244-5 [pii]
AID - 10.1016/j.lungcan.2015.05.008 [doi]
PST - ppublish
SO  - Lung Cancer. 2015 Aug;89(2):189-96. doi: 10.1016/j.lungcan.2015.05.008. Epub 2015 
      May 16.