Human augmenter of liver regeneration is important for hepatoma cell viability and resistance to radiation-induced oxidative stress.
To gain new insight into the biological function of the human augmenter of liver regeneration (hALR) in HCC, we studied its involvement in radiation-induced damage and recovery of HCC cells. We found that hALR expression was up-regulated in both HCC tissues and multiple hepatoma cell lines and correlated significantly with increased radiation clonogenic survival after radiation treatment. Exogenous expression of hALR increased radiation resistance in SMMC-7721 cells, and the increased survival was accompanied by a decrease in apoptosis and a prolonged G(2)-M arrest after irradiation. Overexpression of ALR significantly increased the mitochondrial membrane potential, inhibited cytochrome c release, and opposed the loss of intracellular ATP levels after radiation. Moreover, knockdown of ALR by siRNA resulted in inhibition of viability in the absence of exogenously added oxidative stress and radiation sensitization in HepG2 cells. Importantly, hALR expression was very low in normal hepatocyte L02 cells, and hALR silencing had a minimal effect on L02 viability and radiation sensitivity. These results suggest that human ALR is important for hepatoma cell viability and involved in the protection of hepatoma cells against irradiation-induced damage by its association with mitochondria. Targeting hALR may be a promising novel approach to enhance the radiosensitivity of hepatoma cancers.
Cao
Yan
Y
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Fu
Yu-Long
YL
Yu
Miao
M
Yue
Pei-Bin
PB
Ge
Chang-Hui
CH
Xu
Wang-Xiang
WX
Zhan
Yi-Qun
YQ
Li
Chang-Yan
CY
Li
Wei
W
Wang
Xiao-Hui
XH
Wang
Zhi-Dong
ZD
Li
Yong-Hui
YH
Yang
Xiao-Ming
XM
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003579:Cytochrome Reductases / Q000096:biosynthesis / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism / Q000528:radiation effects; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000528:radiation effects; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011836:Radiation Tolerance; D012189:Retrospective Studies; D015854:Up-Regulation / Q000528:radiation effects
D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors