RNA Binding Motif Protein RBM41 Promotes Colorectal Tumorigenesis by Impeding the Maturation of NDRG1 Pre-mRNA

Background Colorectal cancer (CRC) is a prevalent and highly lethal malignancy whose progression and therapeutic resistance are driven by complex post-transcriptional regulatory mechanisms. RNA-binding motif (RBM) proteins have been demonstrated to play a role in CRC pathogenesis. Methods The functional role of RBM41 was investigated using CRC cell lines, patient-derived organoid (PDO) models, and xenograft tumor experiments in vivo. Molecular mechanisms were explored by examining the interaction between RBM41 and its target mRNA. Results Elevated RBM41 expression in CRC tissues was associated with poor prognosis. Inhibition of RBM41 significantly decreased CRC cell proliferation and induced autophagic cell death and apoptosis. Mechanistically, RBM41 directly binds the 3' untranslated region (3' UTR) of NDRG1 pre-mRNA, inhibiting its processing and reducing mature NDRG1 transcript and protein levels. NDRG1 was found to counteract the oncogenic functions of RBM41, and concurrent knockdown of NDRG1 reversed these effects both in vitro and in vivo. Furthermore, PDO models with high RBM41 expression exhibited increased resistance to 5-fluorouracil, oxaliplatin, and irinotecan. Conclusions RBM41 acts as a key post-transcriptional regulator of CRC progression by repressing NDRG1, highlighting its potential as a therapeutic target in colorectal cancer.