癌症的标志之一是肿瘤细胞的代谢重编程,有氧糖酵解是葡萄糖迅速转化为乳酸的主要机制。作为主要的限速酶之一,丙酮酸激酶(PK)M参与有氧糖酵解的最后阶段。选择性剪接是蛋白质多样性的重要机制,它促进PKM前体mRNA剪接以产生PKM2优势,导致低PKM1表达。特定的剪接同工型在各种组织或疾病情况下产生,翻译后修饰与许多疾病有关,包括癌症。hnRNPs是剪接因子家族的主要组成部分之一。然而,目前还没有关于hnRNPs调节PKM选择性剪接的全面研究。因此,本文就hnRNPs在肿瘤中对PKMpre-mRNA选择性剪接的调控网络及临床药物研究作一综述。我们阐明了选择性剪接在肿瘤进展中的作用,预后,以及异常RNA剪接的潜在机制。我们还总结了延缓肿瘤剪接事件的药物靶点,这对于提高当前治疗干预措施的特异性和有效性可能至关重要。
One of the hallmarks of cancer is metabolic reprogramming in tumor cells, and aerobic glycolysis is the primary mechanism by which glucose is quickly transformed into lactate. As one of the primary rate-limiting enzymes, pyruvate kinase (PK) M is engaged in the last phase of aerobic glycolysis. Alternative splicing is a crucial mechanism for protein diversity, and it promotes PKM precursor mRNA splicing to produce PKM2 dominance, resulting in low PKM1 expression. Specific splicing isoforms are produced in various tissues or illness situations, and the post-translational modifications are linked to numerous disorders, including cancers.
hnRNPs are one of the main components of the splicing factor families. However, there have been no comprehensive studies on
hnRNPs regulating PKM alternative splicing. Therefore, this review focuses on the regulatory network of
hnRNPs on PKM pre-mRNA alternative splicing in tumors and clinical drug research. We elucidate the role of alternative splicing in tumor progression, prognosis, and the potential mechanism of abnormal RNA splicing. We also summarize the drug targets retarding tumorous splicing events, which may be critical to improving the specificity and effectiveness of current therapeutic interventions.