PMID- 27167192
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20211204
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 24
DP  - 2016 Jun 14
TI  - Loss of AIM2 expression promotes hepatocarcinoma progression through activation 
      of mTOR-S6K1 pathway.
PG  - 36185-36197
LID - 10.18632/oncotarget.9154 [doi]
AB  - Absent in melanoma (AIM2) is a member of the interferon-inducible HIN-200 protein 
      family and is recently recognized to play an important dual role in both innate 
      immunity and tumor pathology. However, the role of AIM2 in the development of 
      hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that AIM2 
      expression was significantly decreased in liver cancer tissues, and loss of its 
      expression was significantly correlated with more advanced tumor progression. 
      Exogenous overexpression of AIM2 in HCC cells suppressed mammalian target of 
      rapamycin (mTOR)-S6K1 pathway and further inhibited proliferation, colony 
      formation and invasion of HCC cells. On the contrary, block of AIM2 in HCC cells 
      induced (mTOR)-S6K1 pathway activation and thus promoted HCC progression. 
      Treatment with mTOR pathway inhibitor rapamycin further verified its contribution 
      to HCC progression in AIM2 absent HCC cells. Thus, these data suggested that AIM2 
      played a critical role as a tumor suppressor and might serve as a potential 
      therapeutic target for future development of AIM2-based gene therapy for human 
      liver cancer. This study also paves a new avenue to treat AIM2-deficient cancer 
      by suppression of mTOR.
FAU - Ma, Xiaomin
AU  - Ma X
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Guo, Pengbo
AU  - Guo P
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Qiu, Yumin
AU  - Qiu Y
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Mu, Kun
AU  - Mu K
AD  - Department of Pathology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Zhu, Lihui
AU  - Zhu L
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Zhao, Wei
AU  - Zhao W
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Gastroenterology, Provincial Hospital Affiliated with Shandong 
      University, Jinan 250021, China.
FAU - Han, Lihui
AU  - Han L
AD  - Department of Immunology, Shandong University School of Medicine, Jinan 250012, 
      China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (AIM2 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*genetics/metabolism/pathology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Middle Aged
MH  - RNA Interference
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*genetics/metabolism
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
MH  - Transplantation, Heterologous
PMC - PMC5094992
OTO - NOTNLM
OT  - absent in melanoma 2
OT  - hepatocellular carcinoma
OT  - inflammasome
OT  - mammalian target of rapamycin
OT  - tumor progression
COIS- None of the authors has potential conflicts or financial interests relevant to 
      this manuscript.
EDAT- 2016/05/12 06:00
MHDA- 2017/12/28 06:00
PMCR- 2016/06/14
CRDT- 2016/05/12 06:00
PHST- 2016/01/06 00:00 [received]
PHST- 2016/04/19 00:00 [accepted]
PHST- 2016/05/12 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2016/05/12 06:00 [entrez]
PHST- 2016/06/14 00:00 [pmc-release]
AID - 9154 [pii]
AID - 10.18632/oncotarget.9154 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Jun 14;7(24):36185-36197. doi: 10.18632/oncotarget.9154.