PMID- 25216670
OWN - NLM
STAT- MEDLINE
DCOM- 20160318
LR  - 20220321
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 17
IP  - 3
DP  - 2015 Mar
TI  - Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor 
      aggressiveness.
PG  - 419-29
LID - 10.1093/neuonc/nou220 [doi]
AB  - BACKGROUND: Malignant glioma is an aggressive cancer requiring new therapeutic 
      targets. MicroRNAs (miRNAs) regulate gene expression post transcriptionally and 
      are implicated in cancer development and progression. Deregulated expressions of 
      several miRNAs, specifically hsa-miR-184, correlate with glioma development. 
      METHODS: Bioinformatic approaches were used to identify potential 
      miR-184-regulated target genes involved in malignant glioma progression. This 
      strategy identified a multifunctional nuclease, SND1, known to be overexpressed 
      in multiple cancers, including breast, colon, and hepatocellular carcinoma, as a 
      putative direct miR-184 target gene. SND1 levels were evaluated in patient tumor 
      samples and human-derived cell lines. We analyzed invasion and signaling in vitro 
      through SND1 gain-of-function and loss-of-function. An orthotopic xenograft model 
      with primary glioma cells demonstrated a role of miR-184/SND1 in glioma 
      pathogenesis in vivo. RESULTS: SND1 is highly expressed in human glioma tissue 
      and inversely correlated with miR-184 expression. Transfection of glioma cells 
      with a miR-184 mimic inhibited invasion, suppressed colony formation, and reduced 
      anchorage-independent growth in soft agar. Similar phenotypes were evident when 
      SND1 was knocked down with siRNA. Additionally, knockdown (KD) of SND1 induced 
      senescence and improved the chemoresistant properties of malignant glioma cells. 
      In an orthotopic xenograft model, KD of SND1 or transfection with a miR-184 mimic 
      induced a less invasive tumor phenotype and significantly improved survival of 
      tumor bearing mice. CONCLUSIONS: Our study is the first to show a novel 
      regulatory role of SND1, a direct target of miR-184, in glioma progression, 
      suggesting that the miR-184/SND1 axis may be a useful diagnostic and therapeutic 
      tool for malignant glioma.
CI  - (c) The Author(s) 2014. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Emdad, Luni
AU  - Emdad L
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Janjic, Aleksandar
AU  - Janjic A
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Alzubi, Mohammad A
AU  - Alzubi MA
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Hu, Bin
AU  - Hu B
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Santhekadur, Prasanna K
AU  - Santhekadur PK
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Menezes, Mitchell E
AU  - Menezes ME
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Shen, Xue-Ning
AU  - Shen XN
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Das, Swadesh K
AU  - Das SK
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Sarkar, Devanand
AU  - Sarkar D
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
FAU - Fisher, Paul B
AU  - Fisher PB
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      School of Medicine, Richmond, Virginia (L.E., A.J., M.A.-Z., B.H., P.K.S., 
      M.E.M., X.-N.S., S.K.D., D.S., P.B.F.); VCU Institute of Molecular Medicine, 
      Virginia Commonwealth University, School of Medicine, Richmond, Virginia (L.E., 
      S.K.D., D.S., P.B.F.); VCU Massey Cancer Center, Virginia Commonwealth 
      University, School of Medicine, Richmond, Virginia (L.E., D.S., P.B.F.).
LA  - eng
GR  - R01 CA138540/CA/NCI NIH HHS/United States
GR  - R01CA134721/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140912
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (MIRN184 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.1.- (Endonucleases)
RN  - EC 3.1.- (SND1 protein, human)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*genetics/metabolism/mortality
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - Endonucleases
MH  - Gene Expression Regulation
MH  - Glioma/*genetics/metabolism/mortality
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Mice
MH  - MicroRNAs/*genetics/metabolism
MH  - Neoplasm Invasiveness
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Up-Regulation
PMC - PMC4483100
OTO - NOTNLM
OT  - SND1
OT  - intracranial injection
OT  - invasion
OT  - malignant glioma
OT  - miR-184
EDAT- 2014/09/14 06:00
MHDA- 2016/03/19 06:00
PMCR- 2016/03/01
CRDT- 2014/09/14 06:00
PHST- 2014/02/27 00:00 [received]
PHST- 2014/07/30 00:00 [accepted]
PHST- 2014/09/14 06:00 [entrez]
PHST- 2014/09/14 06:00 [pubmed]
PHST- 2016/03/19 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - nou220 [pii]
AID - 10.1093/neuonc/nou220 [doi]
PST - ppublish
SO  - Neuro Oncol. 2015 Mar;17(3):419-29. doi: 10.1093/neuonc/nou220. Epub 2014 Sep 12.