PMID- 21544242
OWN - NLM
STAT- MEDLINE
DCOM- 20110825
LR  - 20220311
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 4
DP  - 2011 Apr 22
TI  - MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1alpha expression.
PG  - e19139
LID - 10.1371/journal.pone.0019139 [doi]
LID - e19139
AB  - MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important roles 
      in various cellular functions and tumor development. Recent studies have 
      indicated that miR-21 is one of the important miRNAs associated with tumor growth 
      and metastasis, but the role and molecular mechanism of miR-21 in regulating 
      tumor angiogenesis remain to be elucidated. In this study, miR-21 was 
      overexpressed by transfecting pre-miR-21 into human prostate cancer cells and 
      tumor angiogenesis was assayed using chicken chorioallantoic membrane (CAM). We 
      found that overexpression of miR-21 in DU145 cells increased the expression of 
      HIF-1alpha and VEGF, and induced tumor angiogenesis. AKT and extracellular regulated 
      kinases (ERK) 1/2 are activated by miR-21. Inhibition of miR-21 by the antigomir 
      blocked this process. Overexpression of the miR-21 target, PTEN, also inhibited 
      tumor angiogenesis by partially inactivating AKT and ERK and decreasing the 
      expression of HIF-1 and VEGF. The AKT and ERK inhibitors, LY294002 and U0126, 
      suppressed HIF-1alpha and VEGF expression and angiogenesis. Moreover, inhibition of 
      HIF-1alpha expression alone abolished miR-21-inducing tumor angiogenesis, indicating 
      that HIF-1alpha is required for miR-21-upregulated angiogenesis. Therefore, we 
      demonstrate that miR-21 induces tumor angiogenesis through targeting PTEN, 
      leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing 
      HIF-1alpha and VEGF expression; HIF-1alpha is a key downstream target of miR-21 in 
      regulating tumor angiogenesis.
FAU - Liu, Ling-Zhi
AU  - Liu LZ
AD  - Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Li, Chongyong
AU  - Li C
FAU - Chen, Qi
AU  - Chen Q
FAU - Jing, Yi
AU  - Jing Y
FAU - Carpenter, Richard
AU  - Carpenter R
FAU - Jiang, Yue
AU  - Jiang Y
FAU - Kung, Hsiang-Fu
AU  - Kung HF
FAU - Lai, Lihui
AU  - Lai L
FAU - Jiang, Bing-Hua
AU  - Jiang BH
LA  - eng
GR  - R01 CA109460/CA/NCI NIH HHS/United States
GR  - CA109460/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 - 20110422
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chick Embryo
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Immunoblotting
MH  - MicroRNAs/*genetics
MH  - Neovascularization, Pathologic/*genetics
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC3081346
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/05/06 06:00
MHDA- 2011/08/27 06:00
PMCR- 2011/04/22
CRDT- 2011/05/06 06:00
PHST- 2010/12/12 00:00 [received]
PHST- 2011/03/18 00:00 [accepted]
PHST- 2011/05/06 06:00 [entrez]
PHST- 2011/05/06 06:00 [pubmed]
PHST- 2011/08/27 06:00 [medline]
PHST- 2011/04/22 00:00 [pmc-release]
AID - PONE-D-10-06552 [pii]
AID - 10.1371/journal.pone.0019139 [doi]
PST - epublish
SO  - PLoS One. 2011 Apr 22;6(4):e19139. doi: 10.1371/journal.pone.0019139.