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J Biol Chem. 2012 Dec 14;287(51):42856-66. doi: 10.1074/jbc.M112.399923. Epub 2012 Oct 22.

The zinc finger protein ZNF268 is overexpressed in human cervical cancer and contributes to tumorigenesis via enhancing NF-κB signaling.

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1
State Key Laboratory of Virology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430072, China.

Abstract

Cervical cancer is one of the most common tumors affecting women's health worldwide. Although human papillomavirus can be detected in nearly all cases, the mechanism of cervical carcinogenesis remains to be further addressed. Here, we demonstrated that ZNF268, a Krüppel-associated box-containing zinc finger protein, might contribute to the development of cervical cancer. We found that ZNF268b2, an isoform of ZNF268, was overexpressed in human squamous cervical cancer specimens. Knockdown of ZNF268 in cervical cancer cells caused cell cycle arrest at the G(0)/G(1) phase, reduced colony formation, and increased sensitivity to TNFα-induced apoptosis. In addition, HeLa cell growth in xenograft nude mice was suppressed by ZNF268 knockdown, with increased apoptosis. Furthermore, ZNF268b2 was shown to increase NF-κB signaling in vitro and in vivo. Reconstitution of NF-κB activity restored proliferation in ZNF268 knockdown HeLa cells. Of note, we observed a high frequency of NF-κB activation in ZNF268-overexpressing cervical cancer tissues, suggesting a pathological coincidence of ZNF268b2 overexpression and NF-κB activation. Taken together, our results reveal a novel role of ZNF268b2 that contributes to cervical carcinogenesis in part through enhancing NF-κB signaling.

PMID:
23091055
PMCID:
PMC3522282
DOI:
10.1074/jbc.M112.399923
[Indexed for MEDLINE]
Free PMC Article
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