Colorectal cancer (CRC) remains one of the deadliest diseases in the whole world. Cancer recurrence and chemotherapeutic drug resistance limit the overall survival rate of patients with CRC. This study aimed to discover the latent miRNAs and genes associated with oxaliplatin resistance in CRC cells. The study found that miR-1254 is upregulated in oxaliplatin-resistant CRC cell line HCT116-R compared with its parental cell line HCT116 by transcriptome sequencing and small RNA sequencing. Meanwhile, MEGF6 (multiple EGF-like domains 6) was downregulated in HCT116-R cells. Transient transfection of miR-1254 mimics significantly reduced cell apoptosis, increased HCT116 tolerance to oxaliplatin, and enhanced MEGF6 expression. Furthermore, transfection of miR-1254 inhibitor increased apoptosis, decreased HCT116-R tolerance to oxaliplatin, and reduced MEGF6 expression. In addition, transient transfection of SiMEGF6 enhanced HCT116 cell resistance to oxaliplatin and reduced cell apoptosis. In summary, MEGF6 is a latent functional target of miR-1254 in regulating oxaliplatin resistance and apoptosis in human CRC cells, suggesting a potential therapeutic target for CRC.
Keywords: Colorectal cancer; MEGF6; chemoresistance; miR-1254; oxaliplatin.
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