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核转运蛋白α2的沉默抑制人肝细胞癌的细胞生长和存活。

Silencing of karyopherin α2 inhibits cell growth and survival in human hepatocellular carcinoma.

作者信息

Yang Yunfeng, Guo Jian, Hao Yuxia, Wang Fuhua, Li Fengxia, Shuang Shaomin, Wang Junping

机构信息

College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, 030006, Shanxi, China.

Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan, 030012, Shanxi, China.

出版信息

Oncotarget. 2017 May 30;8(22):36289-36304. doi: 10.18632/oncotarget.16749.

Abstract

Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be upregulated in hepatocellular carcinoma and considered as a biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions in hepatocellular carcinogenesis are still lacking. Our study examine the roles and related molecular mechanisms of KPNA2 in hepatocellular carcinoma development. Results show that KPNA2 knockdown inhibited the proliferation and growth of hepatocellular carcinoma cells in vitro and in vivo. KPNA2 knockdown also inhibited colony formation ability, induced cell cycle arrest and cellular apoptosis in two hepatocellular carcinoma cell lines, HepG2 and SMMC-7721. Furthermore, gene expression microarray analysis in HepG2 cells with KPNA2 knockdown revealed that critical signaling pathways involved in cell proliferation and survival were deregulated. In conclusion, this study provided systematic evidence that KPNA2 was an essential factor promoting hepatocellular carcinoma and unraveled potential molecular pathways and networks underlying KPNA2-induced hepatocellular carcinogenesis.

摘要

核转运蛋白α2(KPNA2)参与核质运输,据报道在肝细胞癌中上调,并被视为预后不良的生物标志物。然而,目前仍缺乏对KPNA2在肝细胞癌发生过程中功能的全面研究。我们的研究探讨了KPNA2在肝细胞癌发展中的作用及相关分子机制。结果表明,敲低KPNA2可在体外和体内抑制肝癌细胞的增殖和生长。敲低KPNA2还抑制了两种肝癌细胞系HepG2和SMMC-7721的集落形成能力,诱导细胞周期停滞和细胞凋亡。此外,对敲低KPNA2的HepG2细胞进行基因表达微阵列分析发现,参与细胞增殖和存活的关键信号通路失调。总之,本研究提供了系统证据,表明KPNA2是促进肝细胞癌的关键因素,并揭示了KPNA2诱导肝细胞癌发生的潜在分子途径和网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037e/5482655/28927cfcd42e/oncotarget-08-36289-g001.jpg

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