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微小RNA-1244使非小细胞肺癌A549细胞对顺铂的耐药性敏感。

MiR-1244 sensitizes the resistance of non-small cell lung cancer A549 cell to cisplatin.

作者信息

Li Weili, Wang Wenzhe, Ding Mingjian, Zheng Xiaoliang, Ma Shenglin, Wang Xiaoju

机构信息

Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang People's Republic of China.

Institute of Lung Cancer, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang People's Republic of China.

出版信息

Cancer Cell Int. 2016 Apr 12;16:30. doi: 10.1186/s12935-016-0305-6. eCollection 2016.

Abstract

BACKGROUND

Cisplatin (DDP)-based chemotherapy is the mainstay of first-line therapy for lung cancer. However, their efficacy is often limited by the existence or development of chemoresistance. The aim of this study was to find and investigate the function of miRNAs in cisplatin (DDP)-resistant non-small cell lung cancer (NSCLC) A549 cell.

METHODS

Quantitative real-time PCR assay was employed to compare the differences of miRNA expression in both cisplatin-resistant A549 (A549/DDP) cell and the parental A549 cell. The dysregulated miRNAs were then corrected by transfecting oligonucleotides into A549/DDP cells. The cellular sensitivity to cisplatin, cell apoptosis and migration were conducted by MTT, flow cytometry and cell wound healing assay, respectively.

RESULTS

Both miR-589 and miR-1244 were significantly down-regulated in A549/DDP cell compared to the parental A549, while the expression of miR-182 and miR-224 were increased in A549/DDP cell (P < 0.05). Importantly, transfection of the cisplatin-resistant cells with either miR-589 or miR-1244 resulted in an increased sensitivity to cisplatin, indicating that the dysregulated miRNA may play an important role in chemotherapy resistance in cancer cell. The rescued expression of miRNA also reduced cell invasion and increased apoptosis of A549/DDP cell.

CONCLUSION

The study indicates a crucial role of miR-1244 in the progress of cisplatin resistance of A549. Further understanding of miR-1244-mediated signaling pathways may promote the clinical use of miR-1244 in lung cancer therapy.

摘要

背景

基于顺铂(DDP)的化疗是肺癌一线治疗的主要手段。然而,其疗效常常受到化疗耐药性的存在或发展的限制。本研究的目的是寻找并研究微小RNA(miRNA)在顺铂(DDP)耐药的非小细胞肺癌(NSCLC)A549细胞中的功能。

方法

采用定量实时聚合酶链反应(PCR)检测法比较顺铂耐药的A549(A549/DDP)细胞和亲本A549细胞中miRNA表达的差异。然后通过将寡核苷酸转染到A549/DDP细胞中来校正失调的miRNA。分别采用MTT法、流式细胞术和细胞划痕愈合试验检测细胞对顺铂的敏感性、细胞凋亡和迁移情况。

结果

与亲本A549细胞相比,miR-589和miR-1244在A549/DDP细胞中均显著下调,而miR-182和miR-224在A549/DDP细胞中的表达增加(P<0.05)。重要的是,用miR-589或miR-1244转染顺铂耐药细胞会导致对顺铂的敏感性增加,这表明失调的miRNA可能在癌细胞的化疗耐药中起重要作用。miRNA的挽救性表达还减少了A549/DDP细胞的侵袭并增加了其凋亡。

结论

该研究表明miR-1244在A549顺铂耐药进展中起关键作用。进一步了解miR-1244介导的信号通路可能会促进miR-1244在肺癌治疗中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a1/4828824/ed3bb91b49ca/12935_2016_305_Fig1_HTML.jpg

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