Abstract:
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.
摘要:
癌症是由体内细胞异常生长引起的,每年造成重大死亡。迄今为止,已经开发出有效的治疗方法来根除肿瘤细胞,但是在接受治疗的患者中会出现难以忍受的毒性和耐药性,限制了现有治疗策略的效率。因此,寻找对癌症进展和治疗反应至关重要的新基因是癌症治疗成功的迫切需要.生物信息学和蛋白质组学技术的最新进展允许从历史上的非编码基因组区域鉴定由非规范开放阅读框(ncORF)编码的新型肽类别。令人惊讶的是,许多ncORF表达功能性微蛋白,在人类癌症中起着至关重要的作用。在这次审查中,我们提供了不同ncORF类型的全面描述,具有编码能力和在人类基因组中发现ncORF的技术方法。我们还总结了ncORFs如pTINCR和HOXB-AS3在调节癌症标志中的致癌作用。以及HOXB-AS3和CIP2A-BP等ncORF在癌症诊断和预后中的作用。我们还讨论了AKT-174aa和DDUP等ncORF如何参与抗癌药物反应,以及ncORF作为治疗靶标的潜力被低估。