Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatics and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the carcinogenic role of ncORFs such as pTINCR and HOXB-AS3 in regulating hallmarks of cancer, as well as the roles of ncORFs such as HOXB-AS3 and CIP2A-BP in cancer diagnosis and prognosis. We also discuss how ncORFs such as AKT-174aa and DDUP are involved in anti-cancer drug response and the underestimated potential of ncORFs as therapeutic targets.
癌症源于体内异常细胞增殖，每年导致大量死亡。迄今为止，虽已开发出多种有效清除肿瘤细胞的治疗方法，但治疗过程中可能出现的不可耐受毒性及耐药性问题，限制了现有治疗策略的疗效。因此，探寻对癌症进展和治疗反应至关重要的新基因，已成为实现成功癌症治疗的迫切需求。近期生物信息学与蛋白质组学技术的进步，使得从传统非编码基因组区域中发现一类由非经典开放阅读框（ncORFs）编码的新型肽成为可能。令人惊讶的是，许多ncORFs能够表达功能性微蛋白，这些微蛋白在人类癌症中发挥着关键作用。本综述系统阐述了具有编码能力的不同ncORF类型，以及发现人类基因组中ncORFs的技术方法。我们总结了如pTINCR和HOXB-AS3等ncORFs在调控癌症特征中的致癌作用，以及如HOXB-AS3和CIP2A-BP等ncORFs在癌症诊断与预后评估中的价值。同时探讨了AKT-174aa和DDUP等ncORFs如何参与抗癌药物反应，并分析了ncORFs作为治疗靶点尚未被充分认识的潜力。
肿瘤(癌症)患者之家