Recombinant adenovirus encoding FAT10 small interfering RNA inhibits HCC growth in vitro and in vivo.
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.
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Jingxiang
J
Chen
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Li
L
Yang
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Hongxu
H
Chen
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Tao
T
Yuan
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Menggang
M
Liu
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: pingchen1956@163.com.
Ping
P
Chen
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D014452:Ubiquitins / Q000037:antagonists & inhibitors / Q000235:genetics*
D034741:RNA, Small Interfering; C109184:UBD protein, human; D014452:Ubiquitins
Carcinogenesis; FAT10; HCC; RNA interference; Strategy