PMID- 25888625
OWN - NLM
STAT- MEDLINE
DCOM- 20160317
LR  - 20210614
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 12
DP  - 2015 Apr 30
TI  - A suppressive role of ionizing radiation-responsive miR-29c in the development of 
      liver carcinoma via targeting WIP1.
PG  - 9937-50
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related 
      deaths worldwide, and it has been linked to radiation exposure. As a well-defined 
      oncogene, wild-type p53-induced phosphatase 1 (WIP1) plays an inhibitory role in 
      several tumor suppressor pathways, including p53. WIP1 is amplified and 
      overexpressed in many malignancies, including HCC. However, the underlying 
      mechanisms remain largely unknown. Here, we show that low-dose ionizing radiation 
      (IR) induces miR-29c expression in female mouse liver, while inhibiting its 
      expression in HepG2, a human hepatocellular carcinoma cell line which is used as 
      a model system in this study. miR-29c expression is downregulated in human 
      hepatocellular carcinoma cells, which is inversely correlated with WIP1 
      expression. miR-29c attenuates luciferase activity of a reporter harboring the 
      3'UTR binding motif of WIP1 mRNA. Ectopic expression of miR-29c significantly 
      represses cell proliferation and induces apoptosis and G1 arrest in HepG2. In 
      contrast, the knockdown of miR-29c greatly enhances HepG2 cell proliferation and 
      suppresses apoptosis. The biological effects of miR-29c may be mediated by its 
      target WIP1 which regulates p53 activity via dephosphorylation at Ser-15. 
      Finally, fluorescence in situ hybridization (FISH) and immunohistochemical 
      analyses indicate that miR-29c is downregulated in 50.6% of liver carcinoma 
      tissues examined, whereas WIP1 is upregulated in 45.4% of these tissues. The 
      expression of miR-29c inversely correlates with that of WIP1 in HCC. Our results 
      suggest that the IR-responsive miR-29c may function as a tumor suppressor that 
      plays a crucial role in the development of liver carcinoma via targeting WIP1, 
      therefore possibly representing a target molecule for therapeutic intervention 
      for this disease.
FAU - Wang, Bo
AU  - Wang B
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
AD  - Department of Biochemistry, Qiqihar Medical University, Qiqihar, P.R. China.
FAU - Li, Dongping
AU  - Li D
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
AD  - Department of Biochemistry, Qiqihar Medical University, Qiqihar, P.R. China.
FAU - Sidler, Corinne
AU  - Sidler C
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
FAU - Rodriguez-Juarez, Rocio
AU  - Rodriguez-Juarez R
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
FAU - Singh, Natasha
AU  - Singh N
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
FAU - Heyns, Mieke
AU  - Heyns M
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
FAU - Ilnytskyy, Yaroslav
AU  - Ilnytskyy Y
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
FAU - Bronson, Roderick T
AU  - Bronson RT
AD  - The Dana Farber/Harvard Comprehensive Cancer Center, Boston, Massachusetts, USA.
FAU - Kovalchuk, Olga
AU  - Kovalchuk O
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (MIRN29a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 3.1.3.16 (PPM1D protein, human)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Ppm1d protein, mouse)
RN  - EC 3.1.3.16 (Protein Phosphatase 2C)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/etiology/genetics/pathology
MH  - Cell Growth Processes/genetics/radiation effects
MH  - Down-Regulation
MH  - Female
MH  - HEK293 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/etiology/*genetics/pathology
MH  - Liver Neoplasms, Experimental/etiology/genetics/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics/metabolism
MH  - Neoplasms, Radiation-Induced/etiology/*genetics/pathology
MH  - Phosphoprotein Phosphatases/*genetics/metabolism
MH  - Protein Phosphatase 2C
MH  - Random Allocation
PMC - PMC4496408
OTO - NOTNLM
OT  - WIP1
OT  - hepatocellular carcinoma
OT  - ionizing radiation
OT  - miR-29c
COIS- CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.
EDAT- 2015/04/19 06:00
MHDA- 2016/03/18 06:00
PMCR- 2015/04/30
CRDT- 2015/04/19 06:00
PHST- 2014/10/24 00:00 [received]
PHST- 2015/01/15 00:00 [accepted]
PHST- 2015/04/19 06:00 [entrez]
PHST- 2015/04/19 06:00 [pubmed]
PHST- 2016/03/18 06:00 [medline]
PHST- 2015/04/30 00:00 [pmc-release]
AID - 3157 [pii]
AID - 10.18632/oncotarget.3157 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Apr 30;6(12):9937-50. doi: 10.18632/oncotarget.3157.