GAS5 Inhibits Gastric Cancer Cell Proliferation Partly by Modulating CDK6.
BACKGROUND
As it is not clear whether growth arrest-specific 5 (GAS5) inhibits gastric cancer (GC) cell proliferation by regulating cell cycle, we analyzed the effect of GAS5 on cell cycle regulation of GC cells and explored the underlying mechanism.


METHODS
We measured GAS5 levels in GC tissues and corresponding normal tissues, and analyzed the role of GAS5 in regulation of cell proliferation and cell cycle in GC cells using CCK-8 assay and flow cytometry. We also measured the expression of P21 and CDK6 proteins after transfection of AGS and MGC-803 cells with pLJM-GAS5 and GAS5 siRNA, respectively, by western blotting.


RESULTS
GAS5 expression was significantly lower in GC tissues relative to normal tissues, and its lower expression was correlated with larger tumor size and a more advanced clinical stage of GC. GAS5 induced growth arrest of GC cells through inhibition of G1-S phase translation. The action of GAS5 may be mediated by upregulation of P21 and suppression of CDK6.


CONCLUSIONS
These data enhance our understanding of the important role that GAS5 plays in the molecular etiology of GC and suggest a potential of GAS5 as a new therapeutic target for GC treatment.
Department of General Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, China.
Xiaoqiang
X
Guo
Kaiyuan
K
Deng
Hao
H
Wang
Jiazeng
J
Xia
Ting
T
Shan
Zheng
Z
Liang
Lubing
L
Yao
Shimao
S
Jin
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C561567:GAS5 long non-coding RNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6