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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1016/1050-1738(92)90004-c

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1573-4919

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Knockdown of ZNF403 inhibits cell proliferation an

Authors: Rui Guan XiaoYan Wen Jing Wu Rongqi Duan Huibi Cao Simon Lam Defu Hou Youdong Wang Jim Hu Zhuchu Chen
Publish Date: 2012/02/19
Volume: 365, Issue: 1-2, Pages: 211-222
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Abstract

ZNF403 also known as GGNBP2 gametogenetin binding protein 2 is a highly conserved gene implicated in spermatogenesis However the exact biological function of ZNF403 is not clear In this study we identified the role of ZNF403 in cell proliferation and cellcycle regulation by utilizing short hairpin RNA shRNAmediated knockdown ZNF403specific shRNA expressing helperdependent adenoviral vector HDAdZNF403shRNA was constructed and transduced human cell lines ZNF403 mRNA and protein expression levels were inhibited as evidenced by realtime PCR and western blot analyses Noticeably we found that knockdown of ZNF403 expression suppressed cell proliferation compared to the nontarget shRNA and vector controls Furthermore cellcycle analysis demonstrated that downregulation of ZNF403 promoted G2/M cellcycle arrest in a dosedependent manner Moreover human cellcycle realtime PCR array revealed that ZNF403 knockdown influenced the expression profile of genes in cellcycle regulation Among these genes western blot analysis confirmed the protein upregulation of p21 and downregulation of MCM2 in response to the ZNF403 knockdown Additionally knockdown of ZNF403 also showed an anticarcinogenetic effect on anchorageindependent growth by colony formation assay and tumor cell migration by woundhealing assay with human laryngeal cancer cell line Hep2 cells Altogether our findings suggest an essential role of ZNF403 in cell proliferation and provide a new insight into the function of ZNF403 in regulating the G2/M cellcycle transition

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