The tumor suppressive miR-302c-3p inhibits migration and invasion of hepatocellular carcinoma cells by targeting TRAF4.
The tumor suppressive miR-302c-3p inhibits migration and invasion of hepatocellular carcinoma cells by targeting TRAF4.
复制标题
抑癌miR-302c-3p通过靶向TRAF4抑制肝细胞癌细胞的迁移和侵袭
DOI：
10.7150/jca.25569
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Yang L;Guo Y;Liu X;Wang T;Tong X;Lei K;Wang J;Huang D;Xu Q
MicroRNAs （miRNAs）已被认为是肿瘤发生和发展的关键调节因子。血清miR-302c-3p在hcv相关的肝细胞癌（HCC）中表达明显失调。然而，miR-302c-3p的表达及其在hbv相关HCC中的功能作用很少被研究。在本研究中，我们发现miR-302c-3p在HCC组织中的表达水平与匹配的肿瘤邻近组织相比明显下调。此外，与正常肝细胞系LO2相比，HCC细胞系中检测到miR-302c-3p低表达。miR-302c-3p低表达与HCC患者多发肿瘤淋巴结、静脉浸润及TNM肿瘤分期呈正相关。值得注意的是，我们的随访数据和TCGA数据表明，miR-302c-3p的低表达预示着HCC患者的生存期较差。在功能上，miR-302c-3p过表达抑制MHCC97H细胞的迁移和侵袭。此外，miR-302c-3p敲低对HepG2细胞的这些转移行为表现出相反的作用。MiR-302c-3p通过直接靶向TRAF4 mRNA的3'-UTR负向调节肿瘤坏死因子受体相关因子4 （TRAF4）的丰度。TRAF4在HCC组织中表达上调。HCC标本中TRAF4 mRNA水平与miR-302c-3p表达呈负相关。在机制上，miR-302c-3p抑制了akt介导的HCC细胞上皮-间质转化（EMT）。重要的是，TRAF4修复逆转了miR-302c-3p对akt诱导的EMT和HCC细胞转移的抑制作用。AKT抑制剂MK2206抑制miR-302c-3p敲低诱导的HepG2细胞EMT。综上所述，这些结果表明miR-302c-3p通过靶向TRAF4在HCC中表现出肿瘤抑制作用。抑制miR-302c-3p/TRAF4轴可能作为HCC的治疗靶点。
MicroRNAs (miRNAs) have been recognized as key regulators of tumorigenesis and progression. Serum miR-302c-3p expression is prominently deregulated in HCV-related hepatocellular carcinoma (HCC). However, the expression of miR-302c-3p and its functional role in HBV-related HCC are rarely investigated. In this study, we found that the expression levels of miR-302c-3p were prominently down-regulated in HCC tissues compared to matched tumor-adjacent tissues. Moreover, miR-302c-3p under-expression was detected in HCC cell lines compared to a normal hepatic cell line LO2. Low miR-302c-3p expression was positively correlated with multiple tumor nodes, venous infiltration and advanced TNM tumor stage of HCC patients. Notably, our follow up data and TCGA data demonstrated that low miR-302c-3p expression predicted a poor survival of HCC patients. Functionally, miR-302c-3p overexpression inhibited migration and invasion of MHCC97H cells in vitro. Additionally, miR-302c-3p knockdown showed an opposite effect on these metastatic behaviors of HepG2 cells. MiR-302c-3p negatively regulated tumor necrosis factor receptor associated factor 4 (TRAF4) abundance by directly targeting 3'-UTR of TRAF4 mRNA. The expression of TRAF4 was up-regulated in HCC tissues. The level of TRAF4 mRNA was inversely correlated with miR-302c-3p expression in HCC specimens. Mechanistically, miR-302c-3p restrained AKT-mediated epithelial-mesenchymal transition (EMT) in HCC cells. Importantly, TRAF4 restoration reversed the inhibitory effect of miR-302c-3p on AKT-induced EMT and HCC cell metastasis. MK2206, an AKT inhibitor, inhibited miR-302c-3p knockdown-induced EMT in HepG2 cells. In summary, these results indicate that miR-302c-3p exhibits a tumor suppressive role in HCC by targeting TRAF4. Inhibition of miR-302c-3p/TRAF4 axis may serve as a therapeutic target for HCC.
登录
查看更多内容
MicroRNA-1468 通过激活人肝细胞癌中 PPAR-γ 介导的 AKT 信号传导促进肿瘤进展
DOI：
10.1186/s13046-018-0717-3
发表时间：
2018-03-06
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu Z;Wang Y;Dou C;Sun L;Li Q;Wang L;Xu Q;Yang W;Liu Q;Tu K
通讯作者：
Tu K
癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
影响因子：
3.1
作者：
Wang J;Yang WJ;Sun C;Luan Y;Cheng GH;Li KL;Kong F
通讯作者：
Kong F
MicroRNA-1296 通过靶向 SRPK1 介导的 PI3K/AKT 通路抑制肝细胞癌的转移和上皮间质转化。
影响因子：
37.3
作者：
Xu Q;Liu X;Liu Z;Zhou Z;Wang Y;Tu J;Li L;Bao H;Yang L;Tu K
通讯作者：
Tu K
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin