Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Exp Mol Pathol. 2014 Apr;96(2):207-11. doi: 10.1016/j.yexmp.2014.01.001. Epub 2014 Jan 14.
Hepatocellular carcinoma is an aggressive and rapidly fatal malignancy representing the common cancer worldwide. The specific cellular gene involved in carcinogenesis has not been fully characterized. The ubiquitin-like modifier FAT10, recently reported to be overexpressed in 90% of hepatocellular carcinoma carcinomas, was attributed to transcriptional upregulation upon the loss of p53 and induced chromosome instability in long-term in vitro culture. However, the exact function of FAT10 in hepatocellular carcinoma is not clear. In the present study, we utilized adenovirus-mediated RNA interference to knock down FAT10 expression in hepatocellular carcinoma cells and observed its effects on hepatocellular carcinoma cell growth in vitro and in vivo. The results demonstrated that interference of FAT10 could inhibit cell proliferation by inhibiting the cell cycle S-phase entry and inducing cell apoptosis. In addition, in vivo experiments showed that adenovirus Ad-siRNA/FAT10 significantly suppressed tumor growth and prolonged the lifespan of tumor-bearing mice. These results suggest that knockdown of FAT10 by adenovirus-delivered siRNA may be a promising therapeutical strategy for treatment of hepatocellular carcinoma.
肝细胞癌是一种侵袭性和快速致命的恶性肿瘤，是全球常见的癌症。参与癌变的特定细胞基因尚未完全确定。泛素样修饰物 FAT10 最近报道在 90%的肝细胞癌中过度表达，归因于 p53 缺失时的转录上调，并在长期体外培养中诱导染色体不稳定性。然而，FAT10 在肝细胞癌中的确切功能尚不清楚。在本研究中，我们利用腺病毒介导的 RNA 干扰敲低肝细胞癌细胞中的 FAT10 表达，并观察其对体外和体内肝细胞癌细胞生长的影响。结果表明，干扰 FAT10 可以通过抑制细胞周期 S 期进入和诱导细胞凋亡来抑制细胞增殖。此外，体内实验表明，腺病毒 Ad-siRNA/FAT10 显著抑制肿瘤生长并延长荷瘤小鼠的寿命。这些结果表明，腺病毒介导的 siRNA 敲低 FAT10 可能是治疗肝细胞癌的一种有前途的治疗策略。
