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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

Involvement of RNA-dependent protein kinase (PKR) in maintaining cell proliferation and migration. (A) Cell proliferation and (B) Transwell migration were recorded in real-time in HepG2 human hepatocellular carcinoma cells in which PKR had been knocked down. Error bars indicate standard errors of four replicates.
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f2-ol-08-06-2762: Involvement of RNA-dependent protein kinase (PKR) in maintaining cell proliferation and migration. (A) Cell proliferation and (B) Transwell migration were recorded in real-time in HepG2 human hepatocellular carcinoma cells in which PKR had been knocked down. Error bars indicate standard errors of four replicates.

Mentions: Experiments were conducted in an xCELLigence Real-Time Cell Analyzer (RTCA) DP system (Roche, Mannheim, Germany). The cells were seeded in 16-well plates (4,000 cells in 150 μl medium/well; E-plate 16; Roche), according to the manufacturer’s instructions. The cell index, which is proportional to the number of cells attached to the culturing surface, was recorded in real-time every 1–2 h for up to 3–4 days. For each well, the cell index recorded 4 h after seeding served as the baseline to subsequently obtain the cell index fold changes. The time point of 4 h after seeding was therefore used to indicate time point zero in Fig. 2A. The average fold changes in the cell proliferation index were calculated from at least four replicate experiments, and are shown as the mean ± standard error (SE).


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)

Involvement of RNA-dependent protein kinase (PKR) in maintaining cell proliferation and migration. (A) Cell proliferation and (B) Transwell migration were recorded in real-time in HepG2 human hepatocellular carcinoma cells in which PKR had been knocked down. Error bars indicate standard errors of four replicates.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ol-08-06-2762: Involvement of RNA-dependent protein kinase (PKR) in maintaining cell proliferation and migration. (A) Cell proliferation and (B) Transwell migration were recorded in real-time in HepG2 human hepatocellular carcinoma cells in which PKR had been knocked down. Error bars indicate standard errors of four replicates.
Mentions: Experiments were conducted in an xCELLigence Real-Time Cell Analyzer (RTCA) DP system (Roche, Mannheim, Germany). The cells were seeded in 16-well plates (4,000 cells in 150 μl medium/well; E-plate 16; Roche), according to the manufacturer’s instructions. The cell index, which is proportional to the number of cells attached to the culturing surface, was recorded in real-time every 1–2 h for up to 3–4 days. For each well, the cell index recorded 4 h after seeding served as the baseline to subsequently obtain the cell index fold changes. The time point of 4 h after seeding was therefore used to indicate time point zero in Fig. 2A. The average fold changes in the cell proliferation index were calculated from at least four replicate experiments, and are shown as the mean ± standard error (SE).

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