The significance of PA28γ and U2AF1 in oral mucosal carcinogenesis
The significance of PA28γ and U2AF1 in oral mucosal carcinogenesis
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PA28γ和U2AF1在口腔粘膜癌变中的意义
DOI：
10.1111/odi.13213
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发表时间：
2020
期刊：
影响因子：
3.8
通讯作者：
Qianming
中科院分区：
文献类型：
--
作者：
Fengying Yin;Jiongke Wang;Kui Zhao;Chuan Xin;Yujie Shi;Xin Zeng;Hao Xu;Jing Li（最后通讯）;Qianming
目的蛋白酶体激活物28γ (PA28γ)的上调在包括口腔癌在内的多种恶性肿瘤的癌变过程中起着关键作用。我们旨在筛选PA28γ的相关基因，探讨其在口腔黏膜癌变中的作用。材料与方法采用生物信息学方法筛选PA28γ相关基因。通过免疫组化分析验证其在口腔鳞状细胞癌（OSCC）中的相关性，并检测其在口腔黏膜癌变全过程中的表达水平。采用Kaplan-Meier法估计总生存率，构建Cox模型预测预后。结果筛选到2小核RNA辅助因子1 (small nuclear RNA auxiliary factor 1, U2AF1)，进一步验证了U2AF1与PA28γ在OSCC中的相关性。PA28γ和U2AF1的表达水平从正常到口腔潜在恶性疾病（OPMD）再到OSCC组织逐渐升高。U2AF1高表达患者的总生存期明显缩短，U2AF1与PA28γ联合应用可显著提高预后预测的准确性。结论u2af1和PA28γ可能在OPMD的发展过程中发挥了关键作用，这可能为开发新的治疗策略来预防OPMD的恶性发展提供了新的思路。
ObjectiveProteasome activator 28γ (PA28γ) upregulation plays a critical role in the carcinogenesis of many malignancies, including oral cancer. We aim to screen the related genes of PA28γ and investigate their function in oral mucosa carcinogenesis.Materials and methodsBioinformatics analysis was performed to screen the related genes of PA28γ. Immunohistochemical analysis was carried out to validate their correlation in oral squamous cell carcinoma (OSCC) and detect their expression levels in the whole process of oral mucosa carcinogenesis. The Kaplan–Meier method was used for estimating the overall survival, and the Cox models were constructed to predict the prognosis.ResultsU2 small nuclear RNA auxiliary factor 1 (U2AF1) was screened out, and the correlation between U2AF1 and PA28γ was further validated in OSCC. The expression levels of PA28γ and U2AF1 were gradually increased from normal to oral potentially malignant disorders (OPMD) to OSCC tissues. Overall survival was significantly shorter in patients with high U2AF1 expression and the combined application of U2AF1 and PA28γ notably improved the accuracy of prognosis prediction.ConclusionU2AF1 and PA28γ might play pivotal roles in the progression of OPMD, which may provide insights into the development of new therapeutic strategies to prevent OPMD from becoming malignant.