PMID- 23285024
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20220311
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and 
      invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization.
PG  - e52397
LID - 10.1371/journal.pone.0052397 [doi]
LID - e52397
AB  - Increasing evidence suggests that chromosomal regions containing microRNAs are 
      functionally important in cancers. Here, we show that genomic loci encoding 
      miR-204 are frequently lost in multiple cancers, including ovarian cancers, 
      pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced 
      expression in several cancers and acts as a potent tumor suppressor, inhibiting 
      tumor metastasis in vivo when systemically delivered. We demonstrated that 
      miR-204 exerts its function by targeting genes involved in tumorigenesis 
      including brain-derived neurotrophic factor (BDNF), a neurotrophin family member 
      which is known to promote tumor angiogenesis and invasiveness. Analysis of 
      primary tumors shows that increased expression of BDNF or its receptor 
      tropomyosin-related kinase B (TrkB) parallel a markedly reduced expression of 
      miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression 
      and subsequent activation of the small GTPase Rac1 and actin reorganization 
      through the AKT/mTOR signaling pathway leading to cancer cell migration and 
      invasion. These results suggest that microdeletion of genomic loci containing 
      miR-204 is directly linked with the deregulation of key oncogenic pathways that 
      provide crucial stimulus for tumor growth and metastasis. Our findings provide a 
      strong rationale for manipulating miR-204 levels therapeutically to suppress 
      tumor metastasis.
FAU - Imam, J Saadi
AU  - Imam JS
AD  - Greehey Children's Cancer Research Institute, University of Texas Health Science 
      Center at San Antonio, San Antonio, Texas, USA.
FAU - Plyler, Jason R
AU  - Plyler JR
FAU - Bansal, Hima
AU  - Bansal H
FAU - Prajapati, Suresh
AU  - Prajapati S
FAU - Bansal, Sanjay
AU  - Bansal S
FAU - Rebeles, Jennifer
AU  - Rebeles J
FAU - Chen, Hung-I Harry
AU  - Chen HI
FAU - Chang, Yao-Fu
AU  - Chang YF
FAU - Panneerdoss, Subbarayalu
AU  - Panneerdoss S
FAU - Zoghi, Behyar
AU  - Zoghi B
FAU - Buddavarapu, Kalyan C
AU  - Buddavarapu KC
FAU - Broaddus, Russell
AU  - Broaddus R
FAU - Hornsby, Peter
AU  - Hornsby P
FAU - Tomlinson, Gail
AU  - Tomlinson G
FAU - Dome, Jeffrey
AU  - Dome J
FAU - Vadlamudi, Ratna K
AU  - Vadlamudi RK
FAU - Pertsemlidis, Alexander
AU  - Pertsemlidis A
FAU - Chen, Yidong
AU  - Chen Y
FAU - Rao, Manjeet K
AU  - Rao MK
LA  - eng
GR  - P30 CA054174/CA/NCI NIH HHS/United States
GR  - T32 DK007686/DK/NIDDK NIH HHS/United States
GR  - P30 CA054174-17/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 - 20121221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MIRN204 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RAC1 protein, human)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Actins/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/*genetics
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Genome, Human/*genetics
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasms/*enzymology/*genetics/pathology
MH  - Protein Transport
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - rac1 GTP-Binding Protein/metabolism
PMC - PMC3528651
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/12/21
CRDT- 2013/01/04 06:00
PHST- 2012/06/08 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/12/21 00:00 [pmc-release]
AID - PONE-D-12-17858 [pii]
AID - 10.1371/journal.pone.0052397 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52397. doi: 10.1371/journal.pone.0052397. Epub 2012 Dec 21.