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Human Noxin is an anti‐apoptotic protein in response to DNA damage of A549 non‐small cell lung carcinoma
Author(s) -
Won KyoungJae,
Im JooYoung,
Yun ChaeOk,
Chung KyungSook,
Kim Young Joo,
Lee JungSun,
Jung YoungJin,
Kim BoKyung,
Song Kyung Bin,
Kim YoungHo,
Chun HoKyung,
Jung Kyeong Eun,
Kim MoonHee,
Won Misun
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28600
Subject(s) - dna damage , gene knockdown , apoptosis , microbiology and biotechnology , comet assay , biology , proliferating cell nuclear antigen , cancer research , a549 cell , dna repair , cell growth , dna , biochemistry
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.