p16INK4A-silencing augments DNA damage-induced apoptosis in cervical cancer cells.
p16(INK4A) (p16) has been suggested to be an early biomarker for the detection of cervical cancer. However, its functional role in cervical cancer is not well characterized. In this study, we reported the consistent and significant upregulation of p16 in cervical cancer tissues when compared to both matched non-tumourous tissues of the same patient and normal cervical tissues from non-cancer patients. We have employed p16 small interfering RNA (siRNA) to dissect the role of p16 in cervical carcinogenesis. Although the silencing of p16 was accompanied by the upregulation of p53, p21 and RB in the p16 siRNA-transfected cells, no significant effect on cell cycle progression was observed. When the p16 siRNA-silenced cells were subjected to DNA damage stress including ultraviolet-irradiation and cisplatin treatments, a significantly higher percentage of apoptotic cells could be observed in the p16-siRNA silenced cells compared to control siRNA-treated cells. Moreover, induction of apoptosis was associated with the activation of p53 through phosphorylation, and this process, when studied by gene profiling experiments, involved both the intrinsic and extrinsic apoptotic pathways. The observation that silencing of p16 expression augments DNA damage-induced apoptosis in cervical cancer cells offers alternative strategies for anti-cancer therapies for human cervical cancer.
Lau
W M
WM
Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.
Ho
T H
TH
Hui
K M
KM
D017209:Apoptosis; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D019942:Genes, p16; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
D018076:DNA, Complementary; D034741:RNA, Small Interfering