Downregulation and tumor-suppressive role of XPO5 in hepatocellular carcinoma
Downregulation and tumor-suppressive role of XPO5 in hepatocellular carcinoma
复制标题
DOI：
10.1007/s11010-016-2692-3
复制
发表时间：
2016-04-01
影响因子：
4.3
通讯作者：
Gao, Yong
中科院分区：
文献类型：
--
作者：
Li, Yandong;Wang, Xiao;Gao, Yong
XPO5(Exp5，Exportin-5)是一种主要介导前microRNAs核输出的转运蛋白。最近的研究表明，XPO5可能在一些癌症中发挥关键作用。然而，关于XPO5在肝细胞癌中的作用却知之甚少。在本研究中，我们通过实时定量聚合酶链式反应(qRT-PCR)和免疫组织化学染色研究了XPO5在肝细胞癌中的表达，并对其在肝细胞癌发生发展中的作用进行了功能分析。结果表明，与癌旁肝组织相比，肝细胞癌组织中XPO5的mRNA和蛋白水平均下调。XPO5的异位表达显著抑制了裸鼠的细胞增殖、集落形成、软琼脂生长和致瘤性，而通过RNA干扰抑制XPO5的表达则表现出相反的表型。此外，XPO5基因敲除促进了肝癌细胞的迁移，降低了E-钙粘蛋白和P53的表达。此外，经DAC和TSA处理后，被测试的肝癌细胞中XPO5的mRNA水平上调，提示表观遗传调控可能参与了XPO5的转录。综上所述，我们的研究结果表明，XPO5在肝细胞癌的发生和发展过程中发挥了潜在的肿瘤抑制作用，同时也是治疗肝细胞癌的一个有前景的分子靶点。
XPO5 (Exp5, Exportin-5) is a transporter protein mainly mediating pre-microRNAs' nuclear export. Recent studies have demonstrated that XPO5 may play crucial roles in a few of cancers. However, little is known about XPO5 in hepatocellular carcinoma (HCC). In the present study, we elucidated the expression of XPO5 by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining in HCC samples and conducted several functional analyses to address its effects on HCC development. The results demonstrated that both mRNA and protein levels of XPO5 were downregulated in HCC tissues compared to adjacent non-cancerous livers. Ectopic expression of XPO5 significantly suppressed cell proliferation, colony formation, growth in soft agar, and tumorigenicity in nude mice, whereas knockdown of XPO5 by RNA inference showed opposite phenotypes. Moreover, XPO5 knockdown promoted HCC cell migration and decreased the expression of E-cadherin and p53. Additionally, after treatment with DAC and TSA, the mRNA level of XPO5 was upregulated in HCC cells tested, implicating that epigenetic modulation may be involved in the transcription of XPO5. Collectively, our findings suggest that XPO5 functions as a potential tumor suppressor in the development and progression of HCC as well as a promising molecular target for HCC therapy.