Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Department of Computer Science, School of Interactive Computing, Georgia Institute of Technology, Atlanta, GA, USA.
Int J Oral Sci. 2022 Feb 14;14(1):9. doi: 10.1038/s41368-022-00162-8.
Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.
多聚腺苷酸结合蛋白相互作用蛋白 1（PAIP1）在翻译起始中发挥关键作用，与多种癌症类型相关。然而，其在口腔鳞状细胞癌（OSCC）及其相关特征（如淋巴结转移[LNM]）中的功能和临床意义尚未被描述。在这里，我们使用来自基因表达综合数据库（GEO）、癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC）的可用数据来分析口腔癌中的 PAIP1 表达。公开可用的数据表明，PAIP1 mRNA 和蛋白水平在 OSCC 中增加。在晚期、LNM 和侵袭模式较差的样本中，高 PAIP1 表达更为明显。此外，体外实验表明，PAIP1 敲低减弱了 OSCC 细胞系的集落形成、侵袭性，降低了 MMP9 活性和 SRC 磷酸化。重要的是，我们通过分析患者样本中的 IHC 评分和 CPTAC 数据发现了 PAIP1 与 pSRC 之间的相关性。我们的研究结果表明，PAIP1 可能是 OSCC 伴 LNM 的独立预后因素，也是改善 OSCC 患者预后的合适治疗靶点。
