Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin.
Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.
Department of Biology, Kyung Hee University, Seoul, Korea. shkim@khu.ac.kr
Jin-Hee
JH
Park
Choong-Ryoul
CR
Sihn
Yeon-Su
YS
Lee
Sung-Jae
SJ
Lee
Sang Hoon
SH
Kim
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D001859:Bone Neoplasms / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D051579:Neurogranin / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
D000903:Antibiotics, Antineoplastic; C532399:NGDN protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051579:Neurogranin; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053179:Caspase 7