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Double stranded RNA-dependent protein kinase promotes the tumorigenic phenotype in HepG2 hepatocellular carcinoma cells by activating STAT3.

Wang X, Dong JH, Zhang WZ, Leng JJ, Cai SW, Chen MY, Yang X - Oncol Lett (2014)

Bottom Line: Mouse models with xenograft transplantations also confirmed a tumorigenic role of PKR in HepG2 cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.

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 vitro cellular 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 by in vitro cellular 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.

No MeSH data available.


Related in: MedlinePlus

Tumorigenic role of RNA-dependent protein kinase (PKR) in HepG2 human hepatocellular carcinoma cells. (A) Weight and (B) volume of tumors following the transplantation of control HepG2 cells and HepG2 cells in which PKR had been knocked down. (A) Weight of xenografted tumors 27 days after transplantation. The data from five individual mice are shown as scattered dots, along with the average weight and standard errors. (B) Tumor volume was measured every three days. Error bars signify the standard error of five biological replicates.
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f3-ol-08-06-2762: Tumorigenic role of RNA-dependent protein kinase (PKR) in HepG2 human hepatocellular carcinoma cells. (A) Weight and (B) volume of tumors following the transplantation of control HepG2 cells and HepG2 cells in which PKR had been knocked down. (A) Weight of xenografted tumors 27 days after transplantation. The data from five individual mice are shown as scattered dots, along with the average weight and standard errors. (B) Tumor volume was measured every three days. Error bars signify the standard error of five biological replicates.

Mentions: To examine the role of PKR in tumorigenesis in vivo, xenograft transplantation experiments were performed in mice. Vector-based PKR shRNA was used to prepare the HepG2 cell line that stably expresses shPKR and therefore silences PKR long-term. These cells were then subcutaneously injected into nude mice (CD1−/−). Compared with the transplantation of regular HepG2 cells and HepG2 cells that stably expressed empty vector, transplantation of the cells that stably expressed shPKR resulted in markedly slower tumor growth and smaller tumor size four weeks after transplantation (Fig. 3). This clearly demonstrates that PKR exerts an important role in promoting tumor development in vivo.


Double stranded RNA-dependent protein kinase promotes the tumorigenic phenotype in HepG2 hepatocellular carcinoma cells by activating STAT3.

Wang X, Dong JH, Zhang WZ, Leng JJ, Cai SW, Chen MY, Yang X - Oncol Lett (2014)

Tumorigenic role of RNA-dependent protein kinase (PKR) in HepG2 human hepatocellular carcinoma cells. (A) Weight and (B) volume of tumors following the transplantation of control HepG2 cells and HepG2 cells in which PKR had been knocked down. (A) Weight of xenografted tumors 27 days after transplantation. The data from five individual mice are shown as scattered dots, along with the average weight and standard errors. (B) Tumor volume was measured every three days. Error bars signify the standard error of five biological replicates.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214393&req=5

f3-ol-08-06-2762: Tumorigenic role of RNA-dependent protein kinase (PKR) in HepG2 human hepatocellular carcinoma cells. (A) Weight and (B) volume of tumors following the transplantation of control HepG2 cells and HepG2 cells in which PKR had been knocked down. (A) Weight of xenografted tumors 27 days after transplantation. The data from five individual mice are shown as scattered dots, along with the average weight and standard errors. (B) Tumor volume was measured every three days. Error bars signify the standard error of five biological replicates.
Mentions: To examine the role of PKR in tumorigenesis in vivo, xenograft transplantation experiments were performed in mice. Vector-based PKR shRNA was used to prepare the HepG2 cell line that stably expresses shPKR and therefore silences PKR long-term. These cells were then subcutaneously injected into nude mice (CD1−/−). Compared with the transplantation of regular HepG2 cells and HepG2 cells that stably expressed empty vector, transplantation of the cells that stably expressed shPKR resulted in markedly slower tumor growth and smaller tumor size four weeks after transplantation (Fig. 3). This clearly demonstrates that PKR exerts an important role in promoting tumor development in vivo.

Bottom Line: Mouse models with xenograft transplantations also confirmed a tumorigenic role of PKR in HepG2 cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.

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 vitro cellular 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 by in vitro cellular 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.

No MeSH data available.


Related in: MedlinePlus