Adenoviral-mediated RNA interference targeting URG11 inhibits growth of human hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the second most common malignancy in Asia, with a 5-year survival rate of less than 5% due to high recurrence after surgery and resistance to chemotherapy. A variety of therapeutic interventions to treat HCC, particularly gene therapy, have recently been investigated in tumor model systems to provide a more complete understanding of hepatocarcinogenesis and effectively design therapeutic strategies to treat this disease. In our study, we constructed an adenoviral vector expressing small interfering RNA (siRNA) targeting a newly discovered gene named upregulated gene 11 (URG11). We introduced this vector into HCC cells to investigate the role of URG11 in HCC carcinogenesis. We observed that upon URG11 knockdown, HCC cell proliferation was inhibited through downregulation of several G1-S phase related molecules including cyclin D1 and apoptosis was induced as a result of Bcl-2 downregulation. Besides decreased expression of cyclin D1, CDK4, pRb and Bcl-2, URG11 also suppressed several other proteins including CAPN9, which was identified by cDNA microarray and 2D gel electrophoresis. Moreover, Ad-URG11-siRNA significantly suppressed HCC tumor growth in nude mice. In conclusion, Ad-URG11-siRNA can significantly suppress HCC tumor growth in vitro and in vivo by silencing the URG11 gene, and the use of this vector for gene therapy may represent a novel strategy to treat human HCC.
Fan
Rui
R
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Li
Xiaohua
X
Du
Wenqi
W
Zou
Xue
X
Du
Rui
R
Zhao
Lina
L
Luo
Guanhong
G
Mo
Ping
P
Xia
Lin
L
Pan
Yanglin
Y
Shi
Yongquan
Y
Lian
Zhaorui
Z
Feitelson
Mark A
MA
Nie
Yongzhan
Y
Liu
Jie
J
Fan
Daiming
D
D000256:Adenoviridae / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D015534:Trans-Activators / Q000235:genetics*
D015534:Trans-Activators; C547681:VWCE protein, human