FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2.
FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2.
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FoxD3 调节的 microRNA-137 通过靶向 AKT2 抑制人肝细胞癌的肿瘤生长和转移
DOI：
10.18632/oncotarget.2089
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发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Yun JP
中科院分区：
文献类型：
--
作者：
Liu LL;Lu SX;Li M;Li LZ;Fu J;Hu W;Yang YZ;Luo RZ;Zhang CZ;Yun JP
在人类癌症中经常失调的microRNA与肝癌发生的进展有关。在这里，我们发现microRNA（miR）-137在肝细胞癌（HCC）中显著下调。其表达下降与静脉侵犯、总苞不完整和远处转移有关。多变量分析表明，miR-137是生存不良的独立指标。我们接下来显示，miR-137的过表达在体外抑制细胞增殖、迁移和侵袭。相反，miR-137抑制促进HCC细胞生长。我们还确定AKT 2是miR-137的关键靶点。统计数据显示HCC患者中AKT 2和miR-137表达呈负相关。AKT 2的沉默表型复制了miR-137诱导的表型，而AKT 2的再表达逆转了miR-137的抑制作用。进一步的研究表明miR-137通过抑制AKT 2/mTOR通路发挥其抗肿瘤活性。此外，我们证明FoxD 3直接结合miR-137的启动子并激活其转录。体内研究证实FoxD 3调节的miR-137通过靶向AKT 2抑制HCC生长和转移。总之，我们的研究结果表明，miR-137是HCC预后的有价值的生物标志物，FoxD 3/miR-137/AKT 2调控网络在HCC进展中起着重要作用。
microRNAs, frequently deregulated in human cancer, have been implicated in the progression of hepatocarcinogenesis. Here, we show that microRNA (miR)-137 is significantly down-regulated in hepatocellular carcinoma (HCC). Its decreased expression is associated with vein invasion, incomplete involucrum, and distant metastasis. Multivariate analysis suggests that miR-137 is an independent indicator for poor survival. We next show that over-expression of miR-137 suppresses cell proliferation, migration and invasion in vitro. Conversely, miR-137 inhibition promotes HCC cell growth. We also identify AKT2 as a key target of miR-137 in this context. Statistical data reveal a reverse correlation of AKT2 and miR-137 expression in HCC patients. Silencing of AKT2 phenotypically copied miR-137-induced phenotypes, whereas re-expression of AKT2 reversed the suppressive effects of miR-137. Further investigations showed that miR-137 exerted its anti-tumour activity via inhibiting the AKT2/mTOR pathway. Moreover, we demonstrate that FoxD3 directly binds to the promoter of miR-137 and activates its transcription. In vivo studies confirm that FoxD3-regulated miR-137 inhibited HCC growth and metastasis via targeting AKT2. Together, our findings indicate that miR-137 is a valuable biomarker for HCC prognosis and the FoxD3/miR-137/AKT2 regulatory network plays an important role in HCC progression.
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影响因子：
4.7
作者：
Chen DL;Wang DS;Wu WJ;Zeng ZL;Luo HY;Qiu MZ;Ren C;Zhang DS;Wang ZQ;Wang FH;Li YH;Kang TB;Xu RH
通讯作者：
Xu RH
影响因子：
6.5
作者：
Luo, Chonglin;Tetteh, Paul W.;Eichmueller, Stefan B.
通讯作者：
Eichmueller, Stefan B.
影响因子：
6.2
作者：
Langevin, Scott M.;Stone, Roslyn A.;Bunker, Clareann H.;Lyons-Weiler, Maureen A.;LaFramboise, William A.;Kelly, Lori;Seethala, Raja R.;Grandis, Jennifer R.;Sobol, Robert W.;Taioli, Emanuela
通讯作者：
Taioli, Emanuela
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
HMGA1 靶标 MicroRNA-137 通过直接靶向 FMNL2 抑制小鼠结直肠癌细胞侵袭和转移
影响因子：
29.4
作者：
Liang, Li;Li, Xianzheng;Ding, Yanqing
通讯作者：
Ding, Yanqing