PMID- 27835881
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 51
DP  - 2016 Dec 20
TI  - IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling 
      from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive 
      signaling.
PG  - 85079-85096
LID - 10.18632/oncotarget.13196 [doi]
AB  - IL-37 has been characterized as a fundamental inhibitor of innate immunity and a 
      tumor suppressor in several cancers. However, the molecular mechanism of IL-37 in 
      hepatocellular carcinoma (HCC) is largely unclear. In this study we found IL-37 
      expression was down-regulated in human HCC tissues and cell lines, and was 
      negatively correlated with tumor size, vascular invasion, as well as 
      overall-survial and disease-free survival (OS and DFS) of HCC. Multivariate Cox 
      analysis revealed that IL-37 was an independent prognostic indicator for OS and 
      DFS in HCC. Functional studies further showed that IL-37 overexpression 
      significantly suppressed tumor growth by confining HCC to G2/M cell cycle arrest 
      in vitro and in vivo. Mechanistically, we determined that IL-37 promoted Smad3 
      phospho-isoform signaling conversion from JNK/pSmad3L/c-Myc oncogenic signaling 
      to pSmad3C/p21 tumor-suppressive signaling. Consistently, we detected a 
      significant negative correlation between IL-37 expression and pSmad3L levels in a 
      cohort of HCC biopsies; and the expression of pSmad3L predicted poorer outcome. 
      These data highlight the importance of IL-37 in the cell proliferation and 
      progression of HCC, and suggests that IL-37 may be a valuable biomarker for HCC 
      prognosis.
FAU - Liu, Rui
AU  - Liu R
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Tang, Chengyong
AU  - Tang C
AD  - Department of Clinical Pharmacology, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Shen, Ai
AU  - Shen A
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
AD  - Department of Hepatobiliary Surgery, Chongqing Cancer Institute, Chongqing 
      400030, China.
FAU - Luo, Huating
AU  - Luo H
AD  - Department of Oncology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing 400016, China.
FAU - Wei, Xufu
AU  - Wei X
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Zheng, Daofeng
AU  - Zheng D
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Sun, Chao
AU  - Sun C
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Li, Zhongtang
AU  - Li Z
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Zhu, Di
AU  - Zhu D
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Li, Tingting
AU  - Li T
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
FAU - Wu, Zhongjun
AU  - Wu Z
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400016, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (IL37 protein, human)
RN  - 0 (Interleukin-1)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Smad3 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/mortality
MH  - Cell Cycle Checkpoints
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Hep G2 Cells
MH  - Humans
MH  - Interleukin-1/genetics/*metabolism
MH  - Liver Neoplasms/genetics/*metabolism/mortality
MH  - MAP Kinase Kinase 4/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Middle Aged
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - Signal Transduction
MH  - Smad3 Protein/*metabolism
MH  - Survival Analysis
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - Xenograft Model Antitumor Assays
MH  - rho GTP-Binding Proteins/metabolism
PMC - PMC5356721
OTO - NOTNLM
OT  - IL-37
OT  - JNK/pSmad3L/c-Myc
OT  - TGF-beta
OT  - hepatocellular carcinoma
OT  - pSmad3C/p21
COIS- CONFLICTS OF INTEREST The authors declared no conflicts of interest.
EDAT- 2016/11/12 06:00
MHDA- 2018/02/27 06:00
PMCR- 2016/12/20
CRDT- 2016/11/12 06:00
PHST- 2016/04/01 00:00 [received]
PHST- 2016/10/26 00:00 [accepted]
PHST- 2016/11/12 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/11/12 06:00 [entrez]
PHST- 2016/12/20 00:00 [pmc-release]
AID - 13196 [pii]
AID - 10.18632/oncotarget.13196 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Dec 20;7(51):85079-85096. doi: 10.18632/oncotarget.13196.