Page 35 - 《中国药科大学学报》2026年第2期

第 57 卷第 2 期 黄昕欣，等：RNA 可变剪接机制及其在肿瘤治疗中的研究进展 161

综上所述，调控 RNA 剪接和修饰的药物在肿 18(7): 437-451.
[9] Wilkinson ME, Charenton C, Nagai K. RNA splicing by the
瘤治疗中展现出广阔的应用前景。通过影响剪接
spliceosome[J]. Annu Rev Biochem, 2020, 89: 359-388.
因子和修饰酶的活性，这些药物不仅能克服传统化 [10] Mangilet AF, Weber J, Schüler S, et al. The Arabidopsis U1
疗的耐药问题，还能增强免疫检查点抑制剂的疗 snRNP regulates mRNA 3'-end processing[J]. Nat Plants, 2024,
10(10): 1514-1531.
效，为肿瘤患者带来新的希望。未来研究将优化这
[11] Yin YF, Lu JY, Zhang XC, et al. U1 snRNP regulates chro-
些药物的使用策略，探索联合治疗潜力，为临床提 matin retention of noncoding RNAs[J]. Nature, 2020,
供更有效的解决方案。 580(7801): 147-150.
[12] Jin WX, Wang Y, Liu CP, et al. Structural basis for snRNA
4 总结与展望 recognition by the double-WD40 repeat domain of Gemin5[J].
Genes Dev, 2016, 30(21): 2391-2403.
可变剪接是真核生物基因表达调控的关键机 [13] Matera AG, Wang ZF. A day in the life of the spliceosome[J].
Nat Rev Mol Cell Biol, 2014, 15(2): 108-121.
制，能够通过不同剪接方式产生多种 mRNA 剪接异 [14] Zhan XC, Yan CY, Zhang XF, et al. Structures of the human
构体，增加蛋白质的多样性，并在肿瘤的发生发展 pre-catalytic spliceosome and its precursor spliceosome[J]. Cell
中发挥重要作用。其失调与多种癌症的发生、进展 Res, 2018, 28(12): 1129-1140.
[15] Bartschat S, Samuelsson T. U12 type introns were lost at multi-
和耐药性密切相关。研究表明，剪接因子的突变或 ple occasions during evolution[J]. BMC Genomics, 2010, 11:
表达变化，以及顺式作用元件和反式作用因子的调 106.
控，均参与肿瘤的进展。在肿瘤治疗中，针对可变 [16] Zhang ZW, Will CL, Bertram K, et al. Molecular architecture of
the human 17S U2 snRNP[J]. Nature, 2020, 583(7815): 310-
剪接的策略显示出巨大潜力。例如，剪接因子（如 313.
SF3B1 和 U2AF1）的突变可改变剪接模式，促进癌 [17] Plaschka C, Lin PC, Nagai K. Structure of a pre-catalytic
spliceosome[J]. Nature, 2017, 546(7660): 617-621.
症进展，而靶向这些因子的药物（如 E7107 和异银
[18] Zhang XF, Yan CY, Zhan XC, et al. Structure of the human ac-
杏素）已在临床前模型中显示出抗癌效果。未来需 tivated spliceosome in three conformational states[J]. Cell Res,
要深入理解可变剪接在不同肿瘤中的机制，开发特 2018, 28(3): 307-322.
[19] Fu XD, Ares M. Context-dependent control of alternative splic-
异性药物，并结合高通量技术以支持个性化治疗。
ing by RNA-binding proteins[J]. Nat Rev Genet, 2014, 15(10):
总之，RNA 可变剪接在肿瘤治疗中具有广阔的应用 689-701.
前景，但需要跨学科的合作和持续的研究投入，以 [20] Zhang XF, Zhan XC, Bian T, et al. Structural insights into
branch site proofreading by human spliceosome[J]. Nat Struct
实现从基础研究到临床应用的转化。
Mol Biol, 2024, 31(5): 835-845.
[21] Zhu YJ, Wu WJ, Shao W, et al. SPLICING FACTOR1 is im-
portant in chloroplast development under cold stress[J]. Plant
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