Abstract
Purpose
Our previous experiments have demonstrated that lncRNA UCA1 (UCA1) promoted cisplatin resistance in lung adenocarcinoma (LUAD). This study aimed to explore the potential downstream target genes regulated by UCA1 and how this downstream gene promotes cisplatin resistance in LUAD.
Methods
Here, we measured the expression level of Heme oxygenase1 (HO1) in LUAD cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based on UCA1 overexpression cell lines and UCA1 knockdown cell lines. HO1 was knocked down in the UCA1 overexpression cell line, and HO1 was overexpressed in the UCA1 knockdown cell line, and the half maximal inhibitory concentration (IC50) trends were observed by adding cisplatin containing a certain concentration gradient. Cell functional assays were performed to observe the changes in the biological behavior of HO1 after overexpression and knockdown, and the tumorigenic assay in nude mice was performed to verify the effect of UCA1 in regulating the growth and cisplatin resistance of HO1 on LUAD cells in vivo.
Results
The results showed that HO1 and UCA1 expression were both upregulated in LUAD tissues and LUAD cisplatin-resistant cell lines, and there was a significant positive correlation between the expression of HO1 and UCA1. In vitro experiments showed that HO1 overexpression could reverse the reduced sensitivity to cisplatin caused by UCA1 knockdown in A549/DDP cells, and HO1 knockdown could reduce cisplatin resistance in A549 UCA1 overexpressing cells. Tumorigenic assays in nude mice further confirmed the role of HO1 in the regulation of UCA1 by activating the NRF2/HO1 pathway against LUAD cisplatin resistance.
Conclusion
Our findings suggested that UCA1 regulates HO1 targets the UCA1/NRF2-HO1 pathway to exert cisplatin resistance in LUAD.
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Data availability
The datasets and materials used in the current study are available from the corresponding author upon request.
Change history
03 January 2023
A Correction to this paper has been published: https://doi.org/10.1007/s00432-022-04568-z
Abbreviations
- NSCLC:
-
Non-small cell lung cancer
- SCLC:
-
Small-cell lung cancer
- lncRNA:
-
Long noncoding RNA
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Lung squamous cell carcinoma
- OS:
-
Overall survival
- CCK8:
-
Cell count kit-8
- DDP:
-
Cisplatin
- FBS:
-
Fetal bovine serum
- IC50:
-
Half-maximal inhibitory concentration
- GSEA:
-
Gene set enrichment analysis
- NC:
-
Negative group
- PBS:
-
Phosphate buffer saline
- RPMI-1640:
-
Roswell Park Memorial Institute-1640
- RT-qPCR:
-
Reverse transcription-quantitative polymerase chain reaction
- TCGA:
-
The Cancer Genome Atlas
- GEPIA:
-
Gene expression profiling interactive analysis
- WB:
-
Western blotting
- NRF2:
-
Nuclear-factor (NF)-E2-related factor 2/NFE2L2
- UCA1:
-
Urothelial carcinoma-associated 1
- HO1:
-
Heme oxygenase-1
- SOD1:
-
Superoxide dismutase 1
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Acknowledgements
The authors are grateful to all of the laboratory members for their assistance.
Funding
This study was supported by the Wenzhou Science and Technology Bureau (Y20220130), the National Natural Science Foundation of China (81672088), the Scientific Research Fund of Zhejiang Provincial Education Department (Y202147905), and Zhejiang Provincial Research Center for Cancer Intelligent Diagnosis and Molecular Technology (JBZX-202003).
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WJS and YMW designed the experiments and wrote the manuscript. LLL, CHL and MJZ prepared and analyzed the data. RHW and FGS supervised the project. All authors read and approved the final manuscript.
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Shi, W., Ling, L., Li, C. et al. LncRNA UCA1 promoted cisplatin resistance in lung adenocarcinoma with HO1 targets NRF2/HO1 pathway. J Cancer Res Clin Oncol 149, 1295–1311 (2023). https://doi.org/10.1007/s00432-022-04152-5
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DOI: https://doi.org/10.1007/s00432-022-04152-5