Wang YaTao, Yang XueSi, Yang ZhangQuan, Chen ZiRui, Jiang HaiFeng, Wang YiCong, Shen DongYan, Su GuoQiang
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen,361003, Fujian Province, China.
The Sixth People's Hospital of Luoyang, 471003, Luoyang, Henan Province, China.
J Cancer. 2025 Mar 29;16(7):2233-2249. doi: 10.7150/jca.105120. eCollection 2025.
Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and is the second leading cause of cancer-related deaths globally. Recently, RNA-binding protein 39(RBM39), a critical factor in tumor-targeted mRNA and protein expression, has played a vital role in tumorigenesis and has broad development prospects in clinical treatment and drug research. However, the functional roles of RBM39 in the progression of CRC remain largely unexplored. This study found that RBM39 is notably overexpressed at both the mRNA and protein levels in CRC tissues compared with normal adjacent tissues. RBM39 was identified as a potential therapeutic target for colorectal cancer. Elevated RBM39 mRNA levels in CRC patients indicated worse survival probabilities. We show that RBM39 enhances the proliferation, migration, and invasion ability of CRC cells. Furthermore, we have made an innovative discovery that increased RBM39 inhibits apoptosis in CRC cells. Mechanistically, RNA-seq analysis indicated that RBM39 activates the NF-κB pathway, which plays a pivotal role in driving the malignant biological behaviors of colorectal cancer. Notably, these findings represent a novel contribution to our understanding of the mechanistic underpinnings of CRC, as they have not been previously documented in the literature. In the nude mouse xenograft model, our study demonstrates that the targeted knockdown of RBM39 markedly suppresses tumor formation, highlighting a novel therapeutic strategy for combating colorectal cancer. In conclusion, RBM39 emerges as a promising candidate for clinical diagnosis and targeted treatment of colorectal cancer, with implications for future research in tumor biology and therapeutic strategies.
结直肠癌(CRC)是全球第三大最常被诊断出的癌症,也是癌症相关死亡的第二大主要原因。最近,RNA结合蛋白39(RBM39)作为肿瘤靶向mRNA和蛋白质表达的关键因子,在肿瘤发生过程中发挥了重要作用,在临床治疗和药物研究方面具有广阔的发展前景。然而,RBM39在结直肠癌进展中的功能作用在很大程度上仍未被探索。本研究发现,与相邻正常组织相比,RBM39在结直肠癌组织中的mRNA和蛋白质水平均显著过表达。RBM39被确定为结直肠癌的潜在治疗靶点。结直肠癌患者中RBM39 mRNA水平升高表明生存概率较差。我们发现RBM39增强了结直肠癌细胞的增殖、迁移和侵袭能力。此外,我们有一个创新性的发现,即RBM39的增加抑制了结直肠癌细胞的凋亡。从机制上讲,RNA测序分析表明RBM39激活了NF-κB通路,该通路在驱动结直肠癌的恶性生物学行为中起关键作用。值得注意的是,这些发现为我们理解结直肠癌的机制基础做出了新的贡献,因为它们以前在文献中尚未有记载。在裸鼠异种移植模型中,我们的研究表明,靶向敲低RBM39可显著抑制肿瘤形成,突出了一种对抗结直肠癌的新治疗策略。总之,RBM39有望成为结直肠癌临床诊断和靶向治疗的候选者,对肿瘤生物学和治疗策略的未来研究具有重要意义。