PMID- 26840256
OWN - NLM
STAT- MEDLINE
DCOM- 20170116
LR  - 20211203
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 9
DP  - 2016 Mar 1
TI  - Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer 
      proliferation and invasion by regulating the Hippo signaling pathway.
PG  - 10037-50
LID - 10.18632/oncotarget.7048 [doi]
AB  - Although Cullin 4A (CUL4A) is mutated or amplified in several human cancer types, 
      its role in gastric cancer (GC) and the mechanisms underlying its regulation 
      remain largely uncharacterized. In the present study, we report that the 
      expression of CUL4A significantly correlated with the clinical stage of the tumor 
      and lymph node metastasis, and survival rates were lower in GC patients with 
      higher levels of CUL4A than in patients with lower CUL4A levels. The upregulation 
      of CUL4A promoted GC cell proliferation and epithelial-mesenchymal transition 
      (EMT) by downregulating LATS1-Hippo-YAP signaling. Knocking down CUL4A had the 
      opposite effect in vitro and in vivo. Interestingly, CUL4A expression was 
      inhibited by the microRNAs (miRNAs), miR-9 and miR-137, which directly targeted 
      the 3'-UTR of CUL4A. Overexpression of miR-9 and miR-137 downregulated the 
      CUL4A-LATS1-Hippo signaling pathway and suppressed GC cell proliferation and 
      invasion in vitro. Taken together, our findings demonstrate that perturbations to 
      miR-9/137-CUL4A-Hippo signaling contribute to gastric tumorigenesis, and suggest 
      potential therapeutic targets for the future treatment of GC.
FAU - Deng, Jun
AU  - Deng J
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Lei, Wan
AU  - Lei W
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Xiang, Xiaojun
AU  - Xiang X
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Zhang, Ling
AU  - Zhang L
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Lei, Jun
AU  - Lei J
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Gong, Yu
AU  - Gong Y
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Song, Meijiao
AU  - Song M
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Fang, Ziling
AU  - Fang Z
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Yu, Feng
AU  - Yu F
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Feng, Miao
AU  - Feng M
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Sun, Ze
AU  - Sun Z
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Chen, Jun
AU  - Chen J
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Zhan, Zhengyu
AU  - Zhan Z
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
FAU - Xiong, Jianping
AU  - Xiong J
AD  - Department of Oncology, The First Affiliated Hospital of Nanchang University, 
      Nanchang 330006, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (3' Untranslated Regions)
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (MIRN137 microRNA, human)
RN  - 0 (MIRN92 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/*genetics
MH  - Cullin Proteins/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Lymphatic Metastasis
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*genetics
MH  - Stomach Neoplasms/*genetics/metabolism/pathology
MH  - Transplantation, Heterologous
PMC - PMC4891102
OTO - NOTNLM
OT  - CUL4A
OT  - Hippo
OT  - gastric cancer
OT  - miR-137
OT  - miR-9
COIS- CONFLICTS OF INTEREST The authors state no conflicts of interest.
EDAT- 2016/02/04 06:00
MHDA- 2017/01/17 06:00
PMCR- 2016/03/01
CRDT- 2016/02/04 06:00
PHST- 2015/09/05 00:00 [received]
PHST- 2015/12/07 00:00 [accepted]
PHST- 2016/02/04 06:00 [entrez]
PHST- 2016/02/04 06:00 [pubmed]
PHST- 2017/01/17 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 7048 [pii]
AID - 10.18632/oncotarget.7048 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Mar 1;7(9):10037-50. doi: 10.18632/oncotarget.7048.