NONO is a member of the Drosophila behavior/human splicing (DBHS) family of proteins. NONO is a multifunctional protein that acts as a “molecular scaffold” to carry out versatile biological activities in many aspects of gene regulation, cell proliferation, apoptosis, migration, DNA damage repair, and maintaining cellular circadian rhythm coupled to the cell cycle. Besides these physiological activities, emerging evidence strongly indicates that NONO-altered expression levels promote tumorigenesis. In addition, NONO can undergo various post-transcriptional or post-translational modifications, including alternative splicing, phosphorylation, methylation, and acetylation, whose impact on cancer remains largely to be elucidated. Overall, altered NONO expression and/or activities are a common feature in cancer. This review provides an integrated scenario of the current understanding of the molecular mechanisms and the biological processes affected by NONO in different tumor contexts, suggesting that a better elucidation of the pleiotropic functions of NONO in physiology and tumorigenesis will make it a potential therapeutic target in cancer. In this respect, due to the complex landscape of NONO activities and interactions, we highlight caveats that must be considered during experimental planning and data interpretation of NONO studies.

NONO 是果蝇行为/人类剪接 (DBHS) 蛋白质家族的成员。NONO是一种多功能蛋白，充当“分子支架”，在基因调控、细胞增殖、凋亡、迁移、DNA损伤修复以及维持与细胞周期耦合的细胞昼夜节律等许多方面发挥多种生物活性。除了这些生理活性之外，新出现的证据强烈表明 NONO 表达水平的改变会促进肿瘤发生。此外，NONO可以经历各种转录后或翻译后修饰，包括选择性剪接、磷酸化、甲基化和乙酰化，其对癌症的影响在很大程度上仍有待阐明。总体而言，NONO 表达和/或活性的改变是癌症的一个常见特征。这篇综述提供了目前对不同肿瘤背景下 NONO 影响的分子机制和生物过程的理解的综合情景，表明更好地阐明 NONO 在生理学和肿瘤发生中的多效性功能将使其成为癌症的潜在治疗靶点。在这方面，由于 NONO 活动和相互作用的复杂情况，我们强调在 NONO 研究的实验规划和数据解释过程中必须考虑的注意事项。