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. 2018 Jun;15(6):4885-4889.
doi: 10.3892/etm.2018.6052. Epub 2018 Apr 11.

The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway

Feng Guo  1 , Zhili Cao  1 , Huiqin Guo  1 , Shanqing Li  1
Affiliations

The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway

Feng Guo et al. Exp Ther Med. 2018 Jun.

Abstract

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 (IC50) 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 IC50 of NCI-H1299/DDP cells inhibiting DDP was 127.82 µM, which was significantly higher than that of parental NCI-H1299 cells (IC50=8.40 µM) (P<0.05). si-HOTAIR interference significantly decreased the sensitivity of cells to DDP, the IC50 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.

Keywords: Wnt signaling pathway; drug resistance; lncRNA-HOTAIR; non-small cell lung cancer.

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Figures

Figure 1.
Figure 1.
Detection of the expression level of lncRNA-HOTAIR mRNA in cancer and cancer-adjacent tissues of patients.
Figure 2.
Figure 2.
The relationship between the expression level of lncRNA-HOTAIR mRNA and the overall survival rate.
Figure 3.
Figure 3.
Detection of IC50 of parental cells and drug-resistant cells by CCK-8. ***P<0.001, compared with NC1-H1299.
Figure 4.
Figure 4.
Detection of the expression level of lncRNA-HOTAIR in normal lung fibroblast, lung cancer parental and drug-resistant cells by RT-PCR. *P<0.05, ***P<0.001, compared with MRC-5.
Figure 5.
Figure 5.
Detection of the effect of si-HOTAIR on the IC50 of drug-resistant cell lines by CCK-8. ***P<0.001, compared with si-control.
Figure 6.
Figure 6.
Detection of the effect of si-HOTAIR on drug-resistant proteins by western blot analysis.
Figure 7.
Figure 7.
Detection of the effect of si-HOTAIR on the Wnt signaling pathway by western blot analysis.
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