Faculty of Pharmacy, College UBT, 10000 Prishtina, Kosovo.
Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, 00185 Rome, Italy.
Biochem Pharmacol. 2023 Nov;217:115848. doi: 10.1016/j.bcp.2023.115848. Epub 2023 Oct 7.
All human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in diseases that trigger defects in metabolism, reduced apoptosis, increased proliferation, and progression in almost all tumor types. Metabolic dysregulations and immune dysfunctions are crucial factors in cancer. In this respect, alternative splicing in tumors could be a potential target for therapeutic cancer strategies. Dysregulation of alternative splicing during mRNA maturation promotes carcinogenesis and drug resistance in many cancer types. Alternative splicing (changing the target mRNA 3'UTR binding site) can result in a protein with altered drug affinity, ultimately leading to drug resistance.. Here, we will highlight the function of various alternative splicing factors, how it regulates the reprogramming of cancer cell metabolism, and their contribution to tumor initiation and proliferation. Also, we will discuss emerging therapeutics for treating tumors via abnormal alternative splicing. Finally, we will discuss the challenges associated with these therapeutic strategies for clinical applications.
所有人类基因都经历可变剪接,导致蛋白质的多样性。然而,在某些情况下,可变剪接的异常调节可能导致代谢缺陷、细胞凋亡减少、增殖增加以及几乎所有肿瘤类型的进展的疾病。代谢失调和免疫功能障碍是癌症的关键因素。在这方面,肿瘤中的可变剪接可能是癌症治疗策略的潜在靶点。在许多癌症类型中,mRNA 成熟过程中的可变剪接失调会促进癌症的发生和耐药性。可变剪接(改变靶 mRNA 3'UTR 结合位点)可导致药物亲和力改变的蛋白质,最终导致耐药性。在这里,我们将重点介绍各种可变剪接因子的功能,它如何调节癌细胞代谢的重编程,以及它们对肿瘤起始和增殖的贡献。我们还将讨论通过异常可变剪接治疗肿瘤的新疗法。最后,我们将讨论与这些治疗策略相关的临床应用挑战。