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Holliday 连接点识别蛋白作为口腔癌的预后生物标志物和治疗靶点。

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

机构信息

Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan.

Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto 860‑8555, Japan.

出版信息

Int J Oncol. 2022 Mar;60(3). doi: 10.3892/ijo.2022.5316. Epub 2022 Feb 1.

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.

摘要

由于口腔癌 (OC) 具有高度恶性,且标准治疗方法的疗效有限,因此迫切需要开发新的治疗方法。为了确定新的 OC 诊断和治疗的潜在分子靶标,我们通过基因表达谱筛选了癌抗原,并将重点放在了 Holliday 连接识别蛋白 (HJURP) 上,这是一种哺乳动物着丝粒特异性伴侣。与正常口腔上皮细胞相比,HJURP 在大多数 OC 细胞系和组织中高度表达。组织微阵列分析证实,在 152 份 OC 组织标本中,有 103 份(67.8%)表达了 HJURP,但在正常口腔组织中的表达有限。HJURP 的阳性表达与总生存期较短显著相关(P=0.003)。通过小干扰 RNA 使 HJURP 耗竭,通过抑制细胞周期进程显著抑制 OC 细胞的生长,并诱导 OC 细胞衰老。此外,抑制 HJURP 与 CENP-A 之间的相互作用显著抑制了 OC 细胞的生长。这些结果表明 HJURP 是一种潜在的预后生物标志物,靶向 HJURP 及其分子途径为开发针对 OC 的治疗方法提供了一种新策略。

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