MiR-320a is associated with cisplatin resistance in lung adenocarcinoma and its clinical value in non-small cell lung cancer: A comprehensive analysis based on microarray data
MiR-320a is associated with cisplatin resistance in lung adenocarcinoma and its clinical value in non-small cell lung cancer: A comprehensive analysis based on microarray data
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MiR-320a与肺腺癌顺铂耐药相关及其在非小细胞肺癌中的临床价值：基于微阵列数据的综合分析
DOI：
10.1016/j.lungcan.2020.06.020
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发表时间：
2020-09-01
期刊：
影响因子：
5.3
通讯作者：
Huang, Ming
中科院分区：
文献类型：
--
作者：
Lu, Min;Hu, Chunhong;Huang, Ming
背景：目前，非小细胞肺癌(NSCLC)的治疗主要以手术和化疗为主。尽管在靶向治疗和免疫治疗方面取得了重大进展，但该病的存活率仍然很低，并与化疗耐药有关。以往的研究表明，组蛋白乙酰化和microRNAs(MiRNAs)可能在化疗耐药中发挥重要作用。本研究的目的是寻找与肺腺癌顺铂(DDP)耐药相关的候选miRNAs。方法：采用5-氮-2‘-脱氧胞苷和曲古抑素A体外逆转A549/DDP细胞的耐药性，并利用芯片技术进行miRNA表达谱分析。此外，我们通过基因表达综合芯片(GEO)和肿瘤基因组图谱(TCGA)收集的数据，研究miR-320a的表达与临床特征的相关性，以确定miR-320a在肺腺癌中的临床作用。此外，我们还研究了miR-320a的生物学功能。TargetScanHuman、PicTar2005和Miranda V5.1。结果：与未处理的A549/DDP细胞相比，5-aza-DC能显著抑制A549/DDP细胞的增殖，促进细胞凋亡。TSA不能逆转顺铂耐药。在顺铂耐药逆转过程中，miR-320a表达上调。肺腺癌组miR-320a的表达水平明显低于对照组。对于生物信息学分析，我们发现了一些与细胞周期进展、肿瘤进展、MAPK信号通路和ErbB信号通路有关的靶基因。结论：本研究证实miR-320a在顺铂耐药逆转过程中上调。生物信息学分析结果可能为研究肺腺癌的发病机制提供一种新的方法。
Background: Currently, the main treatment for non-small cell lung cancer (NSCLC) is surgery and chemotherapy. Although major progress has been made in targeted treatment and immunotherapy, the survival rates for this disease are still low and associated with resistance to chemotherapy. Previous studies have shown that histone acetylation and microRNAs (miRNAs) might play an important role in chemotherapy resistance. The aim of this study was to identify candidate miRNAs related to cisplatin (DDP) resistance in lung adenocarcinoma.Methods: We used 5-aza-2'-deoxycytidine and trichostatin A to reverse the drug resistance of A549/DDP cells in vitro, and miRNA expression profiling was performed by microarrays to identify candidate miRNAs. In addition, we investigated the correlations between miR-320a expression and clinical characteristics through data collected from Gene Expression Omnibus (GEO) microarrays, and The Cancer Genome Atlas (TCGA) to determine the clinical role of miR-320a in lung adenocarcinoma. Furthermore, we investigated the biological function of miR-320a. TargetScanHuman, PicTar2005 and miRanda v5.1. were used to predict the target genes of miR-320a; then, the function of these genes were suggested from the enrichment of GO categories items and KEGG analyses.Results: Treatment with 5-Aza-dc significantly inhibited cellular proliferation, and increased apoptosis in the A549/DDP cells compared with the untreated cells. TSA did not reverse cisplatin resistance. MiR-320a was upregulated during reversal of cisplatin resistance. The lung adenocarcinoma groups had a significantly lower level of miR-320a expression than the control groups. For the bioinformatics analyses, we found some target genes involved in cell cycle progression, tumor progression, the MAPK signaling pathway, and the ErbB signaling pathway. The promising target genes were highly enriched in various pathways in cancer.Conclusions: The current study confirmed miR-320a was up-regulated during the revering of cisplatin resistance. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of lung adenocarcinoma.