MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in hepatocellular carcinoma
MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in hepatocellular carcinoma
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MicroRNA-30a 抑制肝细胞癌中自噬介导的失巢凋亡抵抗和转移。
DOI：
10.1016/j.canlet.2017.10.012
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Ding, Zhen-Bin
中科院分区：
文献类型：
--
作者：
Fu, Xiu-Tao;Shi, Ying-Hong;Ding, Zhen-Bin
MiRNA-30 a（miR-30 a）此前被报道为转移性肝细胞癌（HCC）相关microRNA之一。然而，miR-30 a在增强我们对HCC转移的生物学理解方面的功能尚不清楚。本研究证实miR-30 a在肝癌组织和细胞系中表达显著下调，并与肝癌的血管浸润、转移潜能和复发性疾病相关。功能研究证实miR-30 a在已建立的裸鼠肺转移模型中可抑制HCC的转移。此外，miR-30 a在体内和体外均被证明可以阻止肝癌细胞的失巢凋亡抑制。从机制上看，自噬相关蛋白Beclin 1和Atg 5是miR-30 a的直接下游靶点，介导了miR-30 a对肝癌自噬活性的影响。总之，转移性HCC中下调的miR-30 a介导Beclin 1和Atg 5依赖性自噬，其赋予HCC细胞中的失巢凋亡抗性。在此过程中自噬作用的分子基础部分有助于HCC转移，表明通过miR-30 a靶向自噬可能对预防HCC复发/转移具有治疗意义。(C)2017爱思唯尔B. V.保留所有权利。
MiRNA-30a (miR-30a) was previously reported as one of metastatic hepatocellular carcinoma (HCC)-related microRNAs. However, the function of miR-30a on enhancing our biological understanding of HCC metastasis is not clear. This study demonstrated that miR-30a was significantly down-regulated in HCC tissues and cell lines, and was associated with vascular invasion, metastasis potential and recurrent disease in HCC. Functional studies confirmed that miR-30a could inhibit the metastasis of HCC in a well established nude mouse model of lung metastasis. Moreover, miR-30a was proved to prevent anoikis inhibition of HCC cells in vivo and in vitro. Mechanically, autophagy related protein Beclin 1 and Atg5 were direct downstream targets of miR-30a, and mediated autophagy activity influence of miR-30a in HCC. Taken together, downregulated miR-30a in metastatic HCC mediates Beclin 1 and Atg5-dependent autophagy, which confers anoikis resistance in HCC cells. The molecular basis of autophagy action during this process partly contributes to the HCC metastasis, suggesting that targeting autophagy via miR-30a may have therapeutic implications for the prevention of HCC recurrence/metastasis. (C) 2017 Elsevier B.V. All rights reserved.