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Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.

Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.
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Yu L, Sun Y, Li J, Wang Y, Zhu Y, Shi Y, Fan X, Zhou J, Bao Y, Xiao J, Cao K, Cao P,


Yu L, Sun Y, Li J, Wang Y, Zhu Y, Shi Y, Fan X, Zhou J, Bao Y, Xiao J, Cao K, Cao P, (click to view)

Yu L, Sun Y, Li J, Wang Y, Zhu Y, Shi Y, Fan X, Zhou J, Bao Y, Xiao J, Cao K, Cao P,

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Journal of experimental & clinical cancer research : CR 2017 08 1536(1) 110 doi 10.1186/s13046-017-0580-7
Abstract
BACKGROUND
Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear.

METHODS
A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo.

RESULTS
shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis.

CONCLUSION
Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

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