Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression
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Cai Qun Bie1,*, Xu You Liu2,*, Ming Rong Cao3,*, Qiu Yan Huang4, Hui Jun Tang1, Min Wang4, Guo Li Cao4, Ting Zhuang Yi4, Sheng Lan Wu1, Wei Jie Xu4, Shao Hui Tang4
1Department of Gastroenterology, The Affiliated Shenzhen Shajing Hospital, Guangzhou Medical University, Shenzhen, China
2Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
3Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China
4Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, China
*These authors contributed equally to this work
Shao Hui Tang, email: email@example.com
Keywords: IGF-1R, HCC, lentiviral vector, RNA interference, gene therapy
Received: May 02, 2016 Accepted: October 26, 2016 Published: November 02, 2016
The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers. The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated RNA interference (RNAi) as a therapeutic target for HCC. We showed that IGF-1R mRNA was up-regulated in Huh7 and Hep3B cells and human HCC tissues, and that IGF-1R knockdown by RNAi led to decreased proliferation, apoptosis induction, and decreased migration and invasion of Huh7 and Hep3B cells. Further, the in vivo study indicated that IGF-1R knockdown markedly diminished the tumorigenesis and metastasis of Huh7 xenograft. Moreover, the intratumoral administration of lentivirus-IGF-1R siRNA led to significant tumor growth inhibition in an established Huh7 xenograft model. Mechanistic investigations showed that midkine was found to be the most significantly down-regulated protein in Huh7 cells with IGF-1R knockdown, and ectopic overexpression of midkine significantly rescued inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression. Collectively, these data suggest that IGF-1R inhibition by RNAi can significantly suppress HCC growth and invasion at least partially through down-regulating midkine expression, and IGF-1R is a potential target for HCC gene therapy.
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