RNA剪接是在转录组和蛋白质组水平上带来多样性的基本过程。剪接体复合体调节RNA剪接的次要和主要过程。异常调节通常与不同的疾病相关,包括糖尿病,中风,高血压,和癌症。在大多数癌症中,异常调节的选择性RNA剪接(ARS)事件直接影响肿瘤进展,侵入性,并经常导致患者的生存不良。和其他胃肠道恶性肿瘤一样,在肝细胞癌(HCC)中,仅这一项就导致了约75%的肝癌,已经观察到了大量的ARS事件,包括内含子保留,外显子跳跃,存在替代3'-剪接位点(3'SS),和备选5'-拼接站点(5'SS)。这些事件在剪接体和非剪接体复合物基因中报道。分子如MCL1,Bcl-X,和BCL2在不同的同工型可以表现为抗凋亡或促凋亡,使剪接体复合体成为一把双刃剑.此类分子的抗凋亡同工型带来对化疗或基础药物的抗性。然而,相比之下,多发性恶性肿瘤,包括靶向促凋亡的同种型/变体的HCC,有利于凋亡诱导并使化疗有效。在这里,我们讨论不同的拼接事件,像差,和反义寡核苷酸(ASO)在调节肝癌肿瘤发生中的RNA剪接方面具有可能的治疗效果。
RNA splicing is the fundamental process that brings diversity at the transcriptome and proteome levels. The spliceosome complex regulates minor and major processes of RNA splicing. Aberrant regulation is often associated with different diseases, including diabetes, stroke, hypertension, and cancer. In the majority of cancers, dysregulated alternative RNA splicing (ARS) events directly affect tumor progression, invasiveness, and often lead to poor survival of the patients. Alike the rest of the gastrointestinal malignancies, in hepatocellular carcinoma (HCC), which alone contributes to ~ 75% of the liver cancers, a large number of ARS events have been observed, including intron retention, exon skipping, presence of alternative 3\'-splice site (3\'SS), and alternative 5\'-splice site (5\'SS). These events are reported in spliceosome and non-spliceosome complexes genes. Molecules such as MCL1, Bcl-X, and BCL2 in different isoforms can behave as anti-apoptotic or pro-apoptotic, making the spliceosome complex a dual-edged sword. The anti-apoptotic isoforms of such molecules bring in resistance to chemotherapy or cornerstone drugs. However, in contrast, multiple malignant tumors, including HCC that target the pro-apoptotic favoring isoforms/variants favor apoptotic induction and make chemotherapy effective. Herein, we discuss different splicing events, aberrations, and antisense oligonucleotides (ASOs) in modulating RNA splicing in HCC tumorigenesis with a possible therapeutic outcome.