PMID- 22719918
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - An artificial miRNA against HPSE suppresses melanoma invasion properties, 
      correlating with a down-regulation of chemokines and MAPK phosphorylation.
PG  - e38659
LID - 10.1371/journal.pone.0038659 [doi]
LID - e38659
AB  - Ribonucleic acid interference (RNAi) based on microRNA (miRNA) context may 
      provide an efficient and safe therapeutic knockdown effect and can be driven by 
      ribonucleic acid polymerase II (RNAP II). In this study, we designed and 
      synthesized miR155-based artificial miRNAs against heparanase (HPSE) constructed 
      with BLOCK-iT Pol II miR RNAi Expression Vector Kit. The expression levels of 
      HPSE declined significantly in both the mRNA and protein levels in HPSE-miRNA 
      transfected melanoma cells that exhibited reduction of adhesion, migration, and 
      invasion ability in vitro and in vivo. We also observed that HPSE miRNA could 
      inhibit the expressions of chemokines of interleukin-8 (IL8) and chemokine (C-X-C 
      motif) ligand 1 (CXCL1), at both the transcriptional and translational levels. 
      Further study on its probable mechanism declared that down-regulation of IL8 and 
      CXCL1 by HPSE-miRNA may be correlated with reduced growth-factor simulated 
      mitogen-activated kinase (MAPK) phosphorylation including p38 MAPK, c-Jun 
      N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) 1 and 2, 
      which could be rescued by miRNA incompatible mutated HPSE cDNA. In conclusion, we 
      demonstrated that artificial miRNAs against HPSE might serve as an alterative 
      mean of therapy to low HPSE expression and to block the adhesion, invasion, and 
      metastasis of melanoma cells. Furthermore, miRNA-based RNAi was also a powerful 
      tool for gene function study.
FAU - Liu, Xiaoyan
AU  - Liu X
AD  - Department of Dermatology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, People's Republic of China.
FAU - Fang, Hong
AU  - Fang H
FAU - Chen, Hongchao
AU  - Chen H
FAU - Jiang, Xiaoling
AU  - Jiang X
FAU - Fang, Deren
AU  - Fang D
FAU - Wang, Yan
AU  - Wang Y
FAU - Zhu, Dingxian
AU  - Zhu D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120615
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (DNA Primers)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.7.- (RNA Polymerase II)
RN  - EC 3.2.1.- (heparanase)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Western
MH  - Chemokines/*metabolism
MH  - DNA Primers
MH  - *Down-Regulation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression
MH  - Glucuronidase/*genetics
MH  - Humans
MH  - Lung Neoplasms/secondary
MH  - Melanoma/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*genetics
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis
MH  - Neoplasm Invasiveness/*genetics
MH  - Phosphorylation
MH  - RNA Polymerase II/metabolism
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC3376136
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/22 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/06/15
CRDT- 2012/06/22 06:00
PHST- 2011/11/22 00:00 [received]
PHST- 2012/05/08 00:00 [accepted]
PHST- 2012/06/22 06:00 [entrez]
PHST- 2012/06/22 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/06/15 00:00 [pmc-release]
AID - PONE-D-11-23268 [pii]
AID - 10.1371/journal.pone.0038659 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e38659. doi: 10.1371/journal.pone.0038659. Epub 2012 Jun 15.