let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis.
let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis.
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let-7b/g沉默激活AKT信号促进胃癌发生
DOI：
10.1186/s12967-014-0281-3
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发表时间：
2014-10-05
影响因子：
7.4
通讯作者：
To KF
中科院分区：
文献类型：
--
作者：
Kang W;Tong JH;Lung RW;Dong Y;Yang W;Pan Y;Lau KM;Yu J;Cheng AS;To KF
BackgroundAberrant AKT activation contributes to gastric cancer cell survival and chemotherapy resistance, however its regulation is poorly understood. microRNAs have been established to be important regulators in gastric carcinogenesis. Here, we showed the functional role and putative target of let-7b and let-7g (let-7b/g) in gastric carcinogenesis.MethodsThe expression of let-7b/g in gastric cancer cell lines and primary tumors were evaluated by miRNA qRT-PCR. The putative target gene of let-7b/g was explored by TargetScan followed by further validation. Functional analyses including MTT proliferation, monolayer colony formation, cell invasion assays andin vivostudy were performed in both ectopic expression and knockdown approaches.Resultslet-7b/g was found down-regulated in gastric cancer and its downregulation was associated with poor survival and correlated with lymph node metastasis. let-7b/g inhibited AKT2 expression by directly binding to its 3'UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6. AKT2 mRNA expression showed negative correlation with the expression of let-7b/g in primary tumors. Short interfering RNA (siRNA) mediated knockdown of AKT2 phenocopied the tumor-suppressive effects of let-7b/g. Moreover, AKT2 re-expression partly abrogated the growth-inhibitory effect of let-7b/g.ConclusionIn conclusion, our findings reveal decreased let-7b/g contributes to aberrant AKT activation in gastric tumorigenesis and provide a potential therapeutic strategy for gastric cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
11.2
作者：
Dillon RL;Marcotte R;Hennessy BT;Woodgett JR;Mills GB;Muller WJ
通讯作者：
Muller WJ
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
6.4
作者：
Matsushima, Kayoko;Isomoto, Hajime;Kohno, Shigeru
通讯作者：
Kohno, Shigeru
影响因子：
3.8
作者：
Rho HW;Lee BC;Choi ES;Choi IJ;Lee YS;Goh SH
通讯作者：
Goh SH