title: Double stranded RNA-dependent protein kinase promotes the tumorigenic phenotype in HepG2 hepatocellular carcinoma cells by activating STAT3.
abstract: Previously known as a first-response protein upon viral infection and other stress signals, double-stranded RNA-dependent protein kinase (PKR, also termed EIF2AK2) has been found to be differentially expressed in multiple types of tumor, including hepatocellular carcinoma, suggesting that PKR may be involved in tumor initiation and development. However, whether and how PKR promotes or suppresses the development of hepatocellular carcinoma remains controversial. In the present study, PKR expression was investigated using qPCR and western blot analysis, which revealed that PKR expression was upregulated in liver tumor tissues, when compared to that of adjacent normal tissues, which were obtained from four primary liver cancer patients. Furthermore,in vitrocellular assays revealed that PKR exerts a key role in maintaining the proliferation and migration of HepG2 human hepatocellular carcinoma cells. Mouse models with xenograft transplantations also confirmed a tumorigenic role of PKR in HepG2 cells. Furthermore, a transcription factor, signal transducer and activator of transcription 3 (STAT3), was revealed to mediate the tumor-promoting function of PKR in HepG2 cells, as shown byin vitrocellular proliferation and migration assays. In conclusion, the results suggested a tumorigenic role of PKR in liver cancer and a detailed mechanism involving an oncogenic transcription factor, STAT3, is described. Therefore, PKR may present a potential novel therapeutic target for the treatment of liver cancer.
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Dong
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Leng
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Shou-Wang
authors.initials: SW
authors.lastname: Cai
authors.affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Xuerui
authors.initials: X
authors.lastname: Yang
keywords: HepG2; double stranded RNA-dependent protein kinase; hepatocellular carcinoma; signal transducer and activator of transcription 3; tumorigenesis