Holliday junction recognition protein as a prognostic biomarker and therapeutic target for oral cancer

霍利迪连接识别蛋白作为口腔癌的预后生物标志物和治疗靶点

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作者:Bayarbat Tsevegjav, Atsushi Takano, Ming Zhu, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo

Abstract

Since oral cancer (OC) is highly malignant and the efficacy of standard treatments is limited, the development of new therapeutics is urgently awaited. To identify potential molecular targets for new OC diagnosis and therapies, we screened oncoantigens by gene expression profile and focused on Holliday junction recognition protein (HJURP), a mammalian centromere‑specific chaperone. HJURP was found to be highly expressed in the majority of OC cell lines and tissues as compared to normal oral epithelial cells. Tissue microarray analysis confirmed that HJURP was expressed in 103 (67.8%) of 152 OC tissue specimens, but expression in normal oral tissues was limited. Positive HJURP expression was significantly correlated with shorter overall survival (P=0.003). Depletion of HJURP by small‑interfering RNAs dramatically inhibited the growth of OC cells by inhibition of cell cycle progression and induced senescence of OC cells. In addition, inhibition of the interaction between HJURP and CENP‑A significantly suppressed the growth of OC cells. These results indicate that HJURP is a potential prognostic biomarker, and targeting HJURP and its molecular pathway presents a new strategy for the development of treatments against OC.

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