Breast cancer is a prevalent global disease that requires the development of effective therapeutic approaches. The occurrence of 5-fluorouracil (5-FU) resistance in breast cancer is emerging, which urgently needs new way to overcome the obstacle. In this study, we validated that the expression of LINC00467 is up-regulated in the breast cancer patients and breast cancer cells. In addition, the high expression of LINC00467 is associated with the 5-FU resistance of breast cancer cells. Interestingly, LINC00467 induced the homologous recombination (HR) repair via promoting the expression of NBS1 in 5-FU resistant breast cancer cells. Furthermore, miR-205 was validated as a common target of LINC00467 and NBS1, indicating that LINC00467 may induce NBS1 via the miRNA-mRNA target. Importantly, we identified that XBP1, as a transcription factor, induced the expression of LINC00467, which resulted in the enhanced HR efficiency and 5-FU resistance. Silencing XBP1 sensitized the 5-FU resistant breast cancer cells to the 5-FU treatment, whereas the ectopic expression of LINC00467 abrogated the effect of XBP1 silencing. In conclusion, LINC00467 enhances the 5-FU resistance by inducing NBS1-mediated DNA repair. LINC00467 also mediates the function of XBP1 in 5-FU resistance in breast cancer cells.
Keywords: Breast cancer; LINC00467; NBS1; XBP1; miR-205.
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