Objective: To investigate the effects of long non-coding RNA(lncRNA) RP11-770J1.3 and transmembrane protein 25 (TMEM25) on paclitaxel resistance in human breast cancer MCF-7/PR cell line.
Methods: The expression of lncRNA RP11-770J1.3 and TMEM25 in human breast cancer MCF-7(paclitaxel sensitive) and MCF-7/PR(paclitaxel resistant) cells were detected by quantitative RT-PCR. The synthetic interfering fragments of lncRNA RP11-770J1.3 and TMEM25 were transfected into MCF-7/PR cells. Sulforhodamine B assay was used to detect the sensitivity of MCF-7/PR cells to paclitaxel after interference of lncRNA RP11-770J1.3 and TMEM25. The expression of multidrug-resistance genes and proteins were detected by qRT-PCR and Western blot, respectively.
Results: lncRNA RP11-770J1.3 and TMEM25 were highly expressed in MCF-7/PR cells, and were significantly down-regulated after transfection of synthetic interfering fragments. Down-regulation of lncRNA RP11-770J1.3 and TMEM25 enhanced the sensitivity of MCF-7/PR cells to paclitaxel, and inhibited the expression of MRP, BCRP and MDR1/P-gp (all P<0.05). Such effects were more significant when lncRNA RP11-770J1.3 and TMEM25 were both down-regulated (all P<0.05).
Conclusions: lncRNA RP11-770J1.3 and TMEM25 are highly expressed in MCF-7/PR cells, and the down-regulation of lncRNA RP11-770J1.3 and TMEM25 can enhance paclitaxel sensitivity in MCF-7/PR cells.
目的: 探讨长链非编码RNA（lncRNA）RP11-770J1.3和跨膜蛋白25（TMEM25）对紫杉醇耐药人乳腺癌细胞株耐药性的影响。
方法: 利用实时定量PCR检测lncRNA RP11-770J1.3和TMEM25在人乳腺癌细胞MCF-7和紫杉醇耐药细胞株（MCF-7/PR）中的表达。在MCF-7/PR中转染lncRNA RP11-770J1.3和TMEM25的干扰片段，磺酰罗丹明B法检测MCF-7/PR对紫杉醇药物敏感性的变化，并运用实时定量PCR和蛋白质印迹法检测多药耐药相关蛋白（MRP）、乳腺癌耐药蛋白（BCRP）、多药耐药基因1（MDR1）及其编码产物P-gp mRNA和蛋白水平的改变。
结果: lncRNA RP11-770J1.3和TMEM25在MCF-7/PR中表达上调（ P < 0.05或 P < 0.01）。与空白对照组和紫杉醇阴性对照组比较，干扰lncRNA RP11-770J1.3和TMEM25的表达可以提高MCF-7/PR对紫杉醇的药物敏感性，并下调耐药相关基因 MRP、 BCRP、 MDR1及其编码产物P-gp的表达（均 P < 0.05）；与单独干扰lncRNA RP11-770J1.3或TMEM25比较，同时干扰lncRNA RP11-770J1.3和TMEM25的作用更加明显（ P < 0.05）。
结论: MCF-7/PR中lncRNA RP11-770J1.3和TMEM25的表达上调，联合干扰lncRNA RP11-770J1.3和TMEM25的表达可以提高MCF-7/PR对紫杉醇的敏感性。