Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin General Surgery Institute, Tianjin, China.
Mol Carcinog. 2024 Feb;63(2):224-237. doi: 10.1002/mc.23647. Epub 2023 Oct 20.
The majority of patients with advanced colorectal cancer have chemoresistance to oxaliplatin, and studies on oxaliplatin resistance are limited. Our research showed that RNA-binding motif single-stranded interacting protein 1 (RBMS1) caused ferroptosis resistance in tumor cells, leading to oxaliplatin resistance. We employed bioinformatics to evaluate publically accessible data sets and discovered that RBMS1 was significantly upregulated in oxaliplatin-resistant colorectal cancer cells, in tandem with ferroptosis suppression. In vivo and in vitro studies revealed that inhibiting RBMS1 expression caused ferroptosis in colorectal cancer cells, restoring tumor cell sensitivity to oxaliplatin. Mechanistically, this is due to RBMS1 inducing prion protein translation, resulting in ferroptosis resistance in tumor cells. Validation of clinical specimens revealed that RBMS1 is similarly linked to tumor development and a poor prognosis. Overall, RBMS1 is a potential therapeutic target with clinical translational potential, particularly for oxaliplatin chemoresistance in colorectal cancer.
大多数晚期结直肠癌患者对奥沙利铂具有化疗耐药性，而对奥沙利铂耐药性的研究有限。我们的研究表明，RNA 结合基序单链相互作用蛋白 1（RBMS1）导致肿瘤细胞发生铁死亡抵抗，从而导致奥沙利铂耐药性。我们采用生物信息学方法评估了公共可访问的数据集，发现 RBMS1 在奥沙利铂耐药的结直肠癌细胞中显著上调，同时伴随着铁死亡抑制。体内和体外研究表明，抑制 RBMS1 表达会导致结直肠癌细胞发生铁死亡，恢复肿瘤细胞对奥沙利铂的敏感性。其机制在于 RBMS1 诱导朊病毒蛋白的翻译，从而导致肿瘤细胞发生铁死亡抵抗。对临床标本的验证表明，RBMS1 与肿瘤的发生和不良预后同样相关。总的来说，RBMS1 是一个具有临床转化潜力的潜在治疗靶点，特别是针对结直肠癌的奥沙利铂化疗耐药性。
