Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, P. R. China.
Nanjing Anji Biotechnology Co. Ltd., Nanjing, Jiangsu 210009, P. R. China.
J Am Chem Soc. 2020 Apr 8;142(14):6708-6716. doi: 10.1021/jacs.0c00706. Epub 2020 Mar 24.
Several important micropeptides encoded by noncoding RNAs have been identified in recent years; however, there have never been any reports of micropeptides in head and neck squamous cell carcinoma (HNSCC). Here we report the discovery and characterization of a human endogenous peptide named micropeptide inhibiting actin cytoskeleton (MIAC). Comprehensive analysis of the TCGA (The Cancer Genome Atlas) database ( = 500), clinical fresh samples ( = 94), and tissue microarrays ( = 60) revealed that lower MIAC expression is correlated with poor overall survival of HNSCC patients. Meanwhile, RNA-sequencing analysis of 9657 human tissues across 32 cancer types from TCGA cohorts found that MIAC is significantly associated with the progression of 5 other different tumors. Mechanistically, MIAC directly interacts with AQP2 (Aquaporin 2) to inhibit the actin cytoskeleton by regulating SEPT2 (Septin 2)/ITGB4 (Integrin Beta 4) and ultimately suppressing the tumor growth and metastasis of HNSCC. Collectively, the mechanism investigation and evaluation of MIAC activity and highlights that MIAC plays an important role in HNSCC tumorigenesis.
近年来，已经鉴定出几种由非编码 RNA 编码的重要微肽；然而，在头颈部鳞状细胞癌（HNSCC）中从未有过任何微肽的报道。在这里，我们报告了一种名为微肽抑制肌动蛋白细胞骨架（MIAC）的人类内源性肽的发现和特征。对 TCGA（癌症基因组图谱）数据库（=500）、临床新鲜样本（=94）和组织微阵列（=60）的综合分析表明，MIAC 表达较低与 HNSCC 患者的总体生存率较差相关。同时，对来自 TCGA 队列的 32 种不同癌症类型的 9657 个人类组织的 RNA-seq 分析发现，MIAC 与其他 5 种不同肿瘤的进展显著相关。在机制上，MIAC 通过调节 SEPT2（Septin 2）/ITGB4（整合素 Beta 4）直接与 AQP2（水通道蛋白 2）相互作用，抑制肌动蛋白细胞骨架，最终抑制 HNSCC 的肿瘤生长和转移。总之，对 MIAC 活性的机制研究和评估强调了 MIAC 在 HNSCC 肿瘤发生中的重要作用。
