长链非编码RNA HOTAIR通过mir-6807-5p/Egr1轴调节MRP1基因的表达，从而影响肺癌细胞的多药耐药性。

LncRNA HOTAIR regulates the expression of MRP1 gene through the mir-6807-5p/Egr1 axis to affect the multidrug resistance of lung cancer cells.

作者信息

Du Yang, Zhu Shaowei, Liu Xianglu, Sun Yingning, Cui Tingting, Liu Jiupeng, Zhang Weiwei, Shao Shuli

机构信息

Department of Life Science and Agroforestry, Qiqihar University, 42 Wenhua Street, Qiqihar 161006, Heilongjiang Province, China.

Department of Life Science and Agroforestry, Qiqihar University, 42 Wenhua Street, Qiqihar 161006, Heilongjiang Province, China; Key Laboratory of Resistance Gene Engineering and Protection of Biodiversity in Cold Areas, Qiqihar University, 42 Wenhua Street, Qiqihar 161006, Heilongjiang Province, China.

出版信息

Gene. 2025 Mar 10;940:149216. doi: 10.1016/j.gene.2025.149216. Epub 2025 Jan 3.

DOI:10.1016/j.gene.2025.149216

PMID:39756551

Abstract

Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, LncRNA HOTAIR is closely related to MDR in lung cancer, however, the effects of HOTAIR on MRP1 expression and MDR in lung cancer cells (A549/DDP) remain unknown. In this study, the effects of HOTAIR on MRP1 gene expression and MDR in A549/DDP cells were monitored. LncRNA HOTAIR was upregulated in A549/DDP cells, and overexpression of HOTAIR promoted MRP1 expression and MDR development. The opposite trend was observed when HOTAIR was silenced in A549/DDP cells. To uncover the role of LncRNA HOTAIR in the MDR of human lung cancer, the effects of Egr1 on MRP1 gene expression and MDR in A549/DDP cells were monitored. The results showed that Egr1 could bind to the MRP1 promoter at site -53/-42 bp and regulate MRP1 expression. Egr1 knock-down reduced MRP1 expression, while Egr1 overexpression increased it. Further, the results demonstrated that LncRNA HOTAIR mediated the effects of Egr1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, miR-6807-3p exerts its function by targeting the Egr1 3'UTR. In conclusion, the results revealed the novel HOTAIR/miR-6807-3p/Egr1 axis in the regulation of MRP1 expression and MDR in lung cancer cells.

摘要

多药耐药相关蛋白1（MRP1）在癌细胞的多药耐药（MDR）中起关键作用，长链非编码RNA HOTAIR与肺癌的多药耐药密切相关，然而，HOTAIR对肺癌细胞（A549/DDP）中MRP1表达和多药耐药的影响尚不清楚。在本研究中，监测了HOTAIR对A549/DDP细胞中MRP1基因表达和多药耐药的影响。长链非编码RNA HOTAIR在A549/DDP细胞中上调，HOTAIR的过表达促进了MRP1表达和多药耐药的发展。当在A549/DDP细胞中沉默HOTAIR时，观察到相反的趋势。为了揭示长链非编码RNA HOTAIR在人肺癌多药耐药中的作用，监测了Egr1对A549/DDP细胞中MRP1基因表达和多药耐药的影响。结果表明，Egr1可以在-53/-42 bp位点与MRP1启动子结合并调节MRP1表达。敲低Egr1可降低MRP1表达，而过表达Egr1则增加其表达。此外，结果表明长链非编码RNA HOTAIR通过海绵吸附miR-6807-3p介导Egr1对MRP1和多药耐药的影响。此外，miR-6807-3p通过靶向Egr1 3'UTR发挥其功能。总之，结果揭示了在肺癌细胞中调节MRP1表达和多药耐药的新的HOTAIR/miR-6807-3p/Egr1轴。