Singh Vikash, Singh Amandeep, Liu Alvin John, Fuchs Serge Y, Sharma Arun K, Spiegelman Vladimir S
Division of Pediatric Hematology and Oncology, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Department of Pharmacology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Cancers (Basel). 2024 Oct 16;16(20):3502. doi: 10.3390/cancers16203502.
RNA-binding proteins (RBPs) play critical roles in regulating post-transcriptional gene expression, managing processes such as mRNA splicing, stability, and translation. In normal intestine, RBPs maintain the tissue homeostasis, but when dysregulated, they can drive colorectal cancer (CRC) development and progression. Understanding the molecular mechanisms behind CRC is vital for developing novel therapeutic strategies, and RBPs are emerging as key players in this area. This review highlights the roles of several RBPs, including LIN28, IGF2BP1-3, Musashi, HuR, and CELF1, in CRC. These RBPs regulate key oncogenes and tumor suppressor genes by influencing mRNA stability and translation. While targeting RBPs poses challenges due to their complex interactions with mRNAs, recent advances in drug discovery have identified small molecule inhibitors that disrupt these interactions. These inhibitors, which target LIN28, IGF2BPs, Musashi, CELF1, and HuR, have shown promising results in preclinical studies. Their ability to modulate RBP activity presents a new therapeutic avenue for treating CRC. In conclusion, RBPs offer significant potential as therapeutic targets in CRC. Although technical challenges remain, ongoing research into the molecular mechanisms of RBPs and the development of selective, potent, and bioavailable inhibitors should lead to more effective treatments and improved outcomes in CRC.
RNA结合蛋白(RBPs)在调节转录后基因表达、管理诸如mRNA剪接、稳定性和翻译等过程中发挥着关键作用。在正常肠道中,RBPs维持组织稳态,但当失调时,它们可推动结直肠癌(CRC)的发生和发展。了解CRC背后的分子机制对于开发新的治疗策略至关重要,而RBPs正成为该领域的关键角色。本综述强调了几种RBPs,包括LIN28、IGF2BP1 - 3、Musashi、HuR和CELF1在CRC中的作用。这些RBPs通过影响mRNA稳定性和翻译来调节关键癌基因和肿瘤抑制基因。虽然由于RBPs与mRNA的复杂相互作用,靶向RBPs具有挑战性,但药物发现的最新进展已鉴定出破坏这些相互作用的小分子抑制剂。这些靶向LIN28、IGF2BPs、Musashi、CELF1和HuR的抑制剂在临床前研究中已显示出有前景的结果。它们调节RBP活性的能力为治疗CRC提供了一条新的治疗途径。总之,RBPs作为CRC的治疗靶点具有巨大潜力。尽管技术挑战仍然存在,但对RBPs分子机制的持续研究以及选择性、强效和可生物利用抑制剂的开发应会带来更有效的治疗方法,并改善CRC的治疗结果。