He Jin, Qiu Weitao, Li Yonghong, Wei Chaojun, Bai Zhongtian, Jia Jing, Cai Hui
NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, China.
Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, China.
Iran J Public Health. 2023 Jul;52(7):1311-1319. doi: 10.18502/ijph.v52i7.13233.
An apoptosis-resistant state determined by apoptotic protein expression is commonly seen in the initiation, progression, and treatment failure stages of human cancer, and anti-tumor drugs targeting apoptotic proteins have been increasingly developed over the past three decades. However, the frequently alternative splicing of apoptotic proteins diminished the ability of targeting drugs to bind to apoptotic proteins and, consequently, limit the drug efficacy. Currently, accumulating evidence has demonstrated that many alternative splicing events have been associated to apoptosis resistance in different cancers. Therefore, the intervention targeting alternative splicing for regulating tumor cell apoptosis is expected to become a new strategy and new direction of antitumor therapy. Here, we present well established alternative splicing events that occur in different apoptosis-related genes and their modification by several approaches with cancer therapeutic purposes.
由凋亡蛋白表达所决定的抗凋亡状态在人类癌症的起始、进展和治疗失败阶段普遍可见,在过去三十年中,针对凋亡蛋白的抗肿瘤药物不断涌现。然而,凋亡蛋白频繁的可变剪接降低了靶向药物与凋亡蛋白结合的能力,进而限制了药物疗效。目前,越来越多的证据表明,许多可变剪接事件与不同癌症中的凋亡抵抗有关。因此,针对可变剪接进行干预以调节肿瘤细胞凋亡有望成为抗肿瘤治疗的新策略和新方向。在此,我们介绍了在不同凋亡相关基因中发生的成熟可变剪接事件,以及为癌症治疗目的通过几种方法对其进行的修饰。