RNA binding motif protein RBM41 promotes colorectal tumorigenesis by impeding the maturation ofpre-mRNA

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Colorectal cancer (CRC) is a prevalent and highly lethal malignancy. RNA-binding motif (RBM) proteins have been demonstrated in CRC pathogenesis. However, the biological function and regulatory mechanisms ofin CRC remain poorly understood. Here, we demonstrate thatis significantly elevated in CRC tissues and is associated with poor prognosis in patients. Overexpression of RBM41 can enhance the malignant proliferation phenotype of CRC cells; in contrast, inhibition ofsignificantly decreases CRC cell proliferation and induces autophagic cell death and apoptosis in HT29 and SW480 cells. Mechanistically,interferes with the processing of N-myc downregulated gene 1 () pre-mRNA by directly binding to its 3’ untranslated region (3’ UTR), thereby decreasing the mature transcript and protein levels of tumor suppressor. Concurrent knockdown ofreversed the oncogenic functions ofin HT29 cells and in fast-growing xenograft tumors in vivo. Moreover, patient-derived organoid (PDO) models with highexpression exhibited increased resistance to 5-fluorouracil, oxaliplatin, and irinotecan. In summary, our findings demonstrate thatpromotes CRC progression by post-transcriptionally repressing, underscoring its potential as a promising therapeutic target for CRC. Abs1