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.

乳腺癌是一种全球流行的疾病，需要开发有效的治疗方法。乳腺癌中5-氟尿嘧啶（5-FU）耐药现象不断出现，迫切需要新的途径来克服这一障碍。在本研究中，我们验证了LINC00467在乳腺癌患者和乳腺癌细胞中的表达上调。此外，LINC00467的高表达与乳腺癌细胞的5-FU耐药性相关。有趣的是，LINC00467通过促进5-FU耐药乳腺癌细胞中NBS1的表达来诱导同源重组（HR）修复。此外，miR-205被验证为LINC00467和NBS1的共同靶标，表明LINC00467可以通过miRNA-mRNA靶标诱导NBS1。重要的是，我们发现 XBP1 作为转录因子诱导LINC00467的表达，从而导致 HR 效率和 5-FU 抗性增强。沉默XBP1使5-FU耐药乳腺癌细胞对5-FU治疗敏感，而LINC00467的异位表达消除了XBP1沉默的效果。总之，LINC00467通过诱导 NBS1 介导的 DNA 修复来增强 5-FU 耐药性。LINC00467还介导 XBP1 在乳腺癌细胞 5-FU 耐药中的功能。