Human Noxin is an anti-apoptotic protein in response to DNA damage of A549 non-small cell lung carcinoma.
Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA-binding C-domain in RPA1, which mediates DNA metabolic processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen-activated protein kinase (MAPK)/p53 in non-small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA-damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage-induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti-tumor efficacy. Thus, hNoxin is a DNA damage-induced anti-apoptotic protein and potential therapeutic target in cancer.
Medical Genomics Research Center, KRIBB, Daejeon, Korea; Functional Genomics, University of Science and Technology, Daejeon, Korea.
Kyoung-Jae
KJ
Won
Joo-Young
JY
Im
Chae-Ok
CO
Yun
Kyung-Sook
KS
Chung
Young Joo
YJ
Kim
Jung-Sun
JS
Lee
Young-Jin
YJ
Jung
Bo-Kyung
BK
Kim
Kyung Bin
KB
Song
Young-Ho
YH
Kim
Ho-Kyung
HK
Chun
Kyeong Eun
KE
Jung
Moon-Hee
MH
Kim
Misun
M
Won
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000502:physiology* / Q000528:radiation effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C000621244:DDIAS protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012235:Rhodamines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C522175:noxin protein, mouse; C022027:lissamine rhodamine B; D048051:p38 Mitogen-Activated Protein Kinases
DNA damage; UV; apoptosis; hNoxin; target