Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1
Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1
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circ-EPHB4 通过抑制 HIF-1 在肝细胞癌中的抗肿瘤作用
DOI：
10.1002/mc.22976
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发表时间：
2019-06-01
影响因子：
4.6
通讯作者：
Xiao, Jianyong
中科院分区：
文献类型：
--
作者：
Tan, Yuhui;Du, Biaoyan;Xiao, Jianyong
EphB4蛋白在各种类型的肿瘤中起着至关重要的作用。然而，有关CIRC-EphB4(HSA_CIRC_0001730)在肿瘤中的作用的研究很少。本研究旨在探讨CIRC-EphB4的功能及其在肝细胞癌中的调控机制。在肝癌组织中，CIRC-EphB4的表达下调，而在Huh7和HepG2细胞中，CIRC-EphB4的过表达抑制了细胞的活力，诱导了细胞的凋亡，并抑制了细胞的迁移和侵袭。在裸鼠模型中，CIRC-EphB4水平与肿瘤重量、大小和转移灶呈负相关，提示CIRC-EphB4抑制肿瘤的发生、发展和转移。此外，CIRC-EphB4过表达显著影响HIF-1和PI3K-AKT信号通路。HIF-1有可能成为CIRC-EphB4的靶点。通过HIF-1和CIRC-EphB4的高表达，CIRC-EphB4的抗肿瘤作用可能与HIF-1有关。综上所述，CIRC-EphB4是肝细胞癌中的一种肿瘤抑制因子，它通过抑制HIF-1的表达发挥作用。
The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The expression of circ-EPHB4 was found to be downregulated in HCC tumor tissues, whereas circ-EPHB4 overexpression suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in Huh7 and HepG2 cells. circ-EPHB4 levels were negatively correlated with tumor weight, size, and metastasis foci in nude mouse models, suggesting circ-EPHB4 inhibits tumorigenesis, tumor development, and metastasis. In addition, HIF-1 and PI3K-AKT pathways were markedly affected by circ-EPHB4 overexpression. HIF-1 could potentially be the target of circ-EPHB4. By overexpressing both HIF-1 and circ-EPHB4, the antitumor effect of circ-EPHB4 should be most probably correlated with HIF-1. In conclusion, circ-EPHB4 is a tumor inhibitor in HCC and functions by inhibiting HIF-1 expression.