The oncoprotein HBXIP facilitates metastasis of hepatocellular carcinoma cells by activation of MMP15 expression
The oncoprotein HBXIP facilitates metastasis of hepatocellular carcinoma cells by activation of MMP15 expression
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癌蛋白 HBXIP 通过激活 MMP15 表达促进肝细胞癌细胞转移
DOI：
10.2147/cmar.s198783
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Yin, Zhenyu
中科院分区：
文献类型：
--
作者：
Zheng, Sen;Wu, Huita;Yin, Zhenyu
背景：由于肝细胞癌（HCC）的复发和转移率较高，患者的临床治疗效果仍不尽人意。据报道，乙肝病毒X相互作用蛋白（HBXIP）在肿瘤发生过程中发挥着关键作用。
目的：我们旨在揭示HBXIP在HCC转移中的功能意义及潜在机制。
方法：采用细胞Transwell实验、体内转移模型、实时荧光定量聚合酶链反应（real - time PCR）、蛋白质免疫印迹分析（western blot analysis）、荧光素酶报告基因检测以及染色质免疫沉淀实验。
结果：在此，我们检测了HBXIP的表达水平，并明确了其在HCC中的临床意义。我们发现，HBXIP在HCC组织中显著上调，且与HCC患者的血管侵犯、肿瘤转移及较差的预后相关。HBXIP在体外可增强细胞迁移和侵袭能力，在体内可促进HCC转移。此外，我们证实HBXIP通过与原癌基因c - myc结合来增加基质金属蛋白酶15（MMP15）的表达。敲低c - myc可消除HBXIP介导的MMP - 15上调。我们还观察到HCC组织中HBXIP与MMP15的表达呈正相关。
结论：我们的研究结果确立了HBXIP - MMP15调控在HCC转移中的新功能，并表明其有望成为HCC转移的新型预后生物标志物和治疗靶点。
Background: Due to the high recurrence and metastasis rate, the clinical outcomes of patients with hepatocellular carcinoma (HCC) are still unsatisfactory. Hepatitis B virus X-interacting protein (HBXIP) has been reported to play crucial roles in carcinogenesis. Purpose: We aimed to reveal the functional significance and underlying mechanism of HBXIP in HCC metastasis. Methods: Cell transwell assay, in vivo metastasis model, real-time PCR, western blot analysis, luciferase reporter and chromatin immunoprecipitation assays were applied. Results: Here, we detected the HBXIP expression level and determined its clinical significance in HCC. We found that HBXIP was significantly upregulated in HCC tissues, and correlated with vascular invasion, tumor metastasis and worse prognosis of HCC patients. HBXIP enhanced cell migration and invasion in vitro, and promoted the metastasis of HCC in vivo. Furthermore, we confirmed that HBXIP increased MMP15 expression through association with proto-oncogene c-myc. Depletion of c-myc abolished HBXIP-mediated MMP-15 upregulation. We also observed a positive correlation between HBXIP and MMP15 expression in HCC tissues. Conclusion: Our results establish a novel function for HBXIP-MMP15 regulation in HCC metastasis and suggest its candidacy as a new prognostic biomarker and therapeutic target for HCC metastasis.