Liu Jingmei, Han Ping, Gong Jin, Wang Yunwu, Chen Bingxin, Liao Jiazhi, Tian Dean
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Death Discov. 2018 Nov 12;4:102. doi: 10.1038/s41420-018-0099-5. eCollection 2018.
Accumulating evidence indicates that KIAA1199 plays a vital role in tumor progression. However, the role of KIAA1199 in hepatocellular carcinoma (HCC) still remains unknown. In this study, we found that KIAA1199 was upregulated in human HCC tissues and in highly metastatic HCC cell lines. Furthermore, the expression of KIAA1199 was significantly correlated with tumor size and metastasis in HCC. Knockdown of KIAA1199 inhibited cell proliferation and migration in vitro, and suppressed tumorigenicity and lung metastasis in vivo. In addition, silencing of KIAA1199 induced G1 phase arrest by reducing cyclinD1 expression. Moreover, KIAA1199 knockdown induced apoptosis by activating endoplasmic reticulum (ER) stress, which was based on the upregulation of ER stress markers, activating transcription factor 4 (ATF4) and CAAT/enhancer-binding protein homologous protein (CHOP). In conclusion, our data demonstrated that KIAA1199 knockdown inhibited the growth and metastasis of HCC.
越来越多的证据表明，KIAA1199在肿瘤进展中起着至关重要的作用。然而，KIAA1199在肝细胞癌（HCC）中的作用仍然未知。在本研究中，我们发现KIAA1199在人类HCC组织和高转移性HCC细胞系中上调。此外，KIAA1199的表达与HCC中的肿瘤大小和转移显著相关。敲低KIAA1199在体外抑制细胞增殖和迁移，并在体内抑制致瘤性和肺转移。此外，沉默KIAA1199通过降低细胞周期蛋白D1的表达诱导G1期阻滞。此外，敲低KIAA1199通过激活内质网（ER）应激诱导细胞凋亡，这是基于ER应激标志物、激活转录因子4（ATF4）和CAAT/增强子结合蛋白同源蛋白（CHOP）的上调。总之，我们的数据表明敲低KIAA1199可抑制HCC的生长和转移。
