Guo Feng, Cao Zhili, Guo Huiqin, Li Shanqing
Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, P.R. China.
Exp Ther Med. 2018 Jun;15(6):4885-4889. doi: 10.3892/etm.2018.6052. Epub 2018 Apr 11.
The action mechanism of long non-coding ribonucleic acid-homeobox transcript antisense ribonucleic acid (lncRNA-HOTAIR) in the regulation of the Wnt signaling pathway on the drug resistance of non-small cell lung cancer was investigated. Forty eight patients with non-small cell lung cancer, who were treated with cisplatin (DDP) as neoadjuvant chemotherapy, were selected from the specimen bank of the Department of Pathology of Peking Union Medical College Hospital. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger RNA (mRNA) level of lncRNA-HOTAIR in cancer and cancer-adjacent tissues. The correlation curve of the expression of lncRNA-HOTAIR with the overall survival (OS) was plotted using the Kaplan-Meier method. NCI-H1299 DDP-resistant cell lines were constructed, and the half maximal inhibitory concentration (IC) value was measured. The expression of lnc-HOTAIR in NCI-H1299/DDP cells was detected by the target interference of small interfering RNA (siRNA). The effect of si-HOTAIR on cell resistance was detected by Cell Counting Kit-8 (CCK-8). Western blot analysis was used to detect the effects of si-HOTAIR on multidrug resistance proteins, multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 1 (MDR1), and Wnt signaling pathways, Wnt3a, adenomatous polyposis coli (APC) and β-catenin. The mRNA level of lncRNA-HOTAIR in cancer tissues was significantly higher than that in cancer-adjacent tissues (P<0.05), and the high expression of lncRNA-HOTAIR indicated that the OS of patients was shortened (P<0.05). The IC of NCI-H1299/DDP cells inhibiting DDP was 127.82 µM, which was significantly higher than that of parental NCI-H1299 cells (IC=8.40 µM) (P<0.05). si-HOTAIR interference significantly decreased the sensitivity of cells to DDP, the IC of cells was decreased from 131.85 to 44.34 µM (P<0.05), the expression levels of MRP1 and MDR1 were significantly decreased, and the activation of Wnt signaling pathway was significantly inhibited (P<0.05). Thus, lncRNA-HOTAIR plays an important role in the occurrence and development of non-small cell lung cancer, and it may be an important factor in the clinical prognosis of patients with non-small cell lung cancer.
研究了长链非编码核糖核酸-同源盒转录反义核糖核酸（lncRNA-HOTAIR）在调控Wnt信号通路对非小细胞肺癌耐药性中的作用机制。从北京协和医院病理科标本库中选取48例接受顺铂（DDP）新辅助化疗的非小细胞肺癌患者。采用逆转录-聚合酶链反应（RT-PCR）检测癌组织和癌旁组织中lncRNA-HOTAIR的信使核糖核酸（mRNA）水平。采用Kaplan-Meier法绘制lncRNA-HOTAIR表达与总生存期（OS）的相关曲线。构建NCI-H1299 DDP耐药细胞系，并测定半数最大抑制浓度（IC）值。通过小干扰RNA（siRNA）的靶向干扰检测NCI-H1299/DDP细胞中lnc-HOTAIR的表达。采用细胞计数试剂盒-8（CCK-8）检测si-HOTAIR对细胞耐药性的影响。采用蛋白质免疫印迹分析检测si-HOTAIR对多药耐药蛋白、多药耐药相关蛋白1（MRP1）和多药耐药蛋白1（MDR1）以及Wnt信号通路、Wnt3a、腺瘤性息肉病大肠杆菌（APC）和β-连环蛋白的影响。癌组织中lncRNA-HOTAIR的mRNA水平显著高于癌旁组织（P<0.05），lncRNA-HOTAIR的高表达表明患者的OS缩短（P<0.05）。NCI-H1299/DDP细胞抑制DDP的IC为127.82 μM，显著高于亲本NCI-H1299细胞（IC=8.40 μM）（P<0.05）。si-HOTAIR干扰显著降低细胞对DDP的敏感性，细胞的IC从131.85降至44.34 μM（P<0.05），MRP1和MDR1的表达水平显著降低，Wnt信号通路的激活受到显著抑制（P<0.05）。因此，lncRNA-HOTAIR在非小细胞肺癌的发生发展中起重要作用，可能是影响非小细胞肺癌患者临床预后的重要因素。
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