Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Internal Medicine, Division of Hematology and Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2021 Feb 27;22(5):2402. doi: 10.3390/ijms22052402.
Most patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly associated with carcinogenesis and treatment outcomes in oral squamous cell cancer, affecting cell growth and proliferation. Therefore, focusing on DNA repair and genetic instability interactions could be a potential target for improving the outcomes of OSCC patients. DNA polymerase-β (POLB) is an important enzyme in base excision repair and contributes to gene instability, leading to tumorigenesis and cancer metastasis. The aim of our study was to confirm POLB regulates the growth of OSCC cells through modulation of cell cycle and chromosomal instability. We analyzed a tissue array from 133 OSCC patients and discovered that low POLB expression was associated with advanced tumor stage and poor overall survival. In multivariate Cox proportional hazards regression analysis, low POLB expression and advanced lymph node status were significantly associated with poor survival. By performing in vitro studies on model cell lines, we demonstrated that POLB silencing regulated cell cycles, exacerbated mitotic abnormalities and enhanced cell proliferation. After POLB depletion, OSCC cells showed chromosomal instability and aneuploidy. Thus, POLB is an important maintainer of karyotypic stability in OSCC cells.
大多数口腔鳞状细胞癌（OSCC）患者在诊断时已处于局部晚期。治疗策略多种多样，包括手术、放疗和化疗。尽管采用了多模式治疗，但反应率仍不理想。DNA 修复和遗传不稳定性与口腔鳞状细胞癌的致癌作用和治疗结果高度相关，影响细胞生长和增殖。因此，关注 DNA 修复和遗传不稳定性的相互作用可能是改善 OSCC 患者治疗效果的一个潜在靶点。DNA 聚合酶-β（POLB）是碱基切除修复中的重要酶，有助于基因不稳定性，导致肿瘤发生和癌症转移。我们的研究旨在证实 POLB 通过调节细胞周期和染色体不稳定性来调控 OSCC 细胞的生长。我们分析了 133 例 OSCC 患者的组织芯片，发现 POLB 低表达与肿瘤晚期和总体生存率差有关。在多变量 Cox 比例风险回归分析中，POLB 低表达和淋巴结转移进展与生存不良显著相关。通过对模型细胞系进行体外研究，我们证明了 POLB 沉默调节细胞周期，加剧有丝分裂异常并增强细胞增殖。POLB 耗竭后，OSCC 细胞表现出染色体不稳定性和非整倍性。因此，POLB 是 OSCC 细胞中核型稳定性的重要维持者。
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