Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray
Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray
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通过微阵列对肺腺癌 EGFR-TKI 耐药中的长非编码 RNA 表达模式进行全基因组分析
DOI：
10.3892/or.2016.4758
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发表时间：
2016-06-01
期刊：
影响因子：
4.2
通讯作者：
Feng, Ji-Feng
中科院分区：
文献类型：
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作者：
Wu, Ying;Yu, Dan-Dan;Feng, Ji-Feng
表皮生长因子受体(EGFR)的突变使肺腺癌细胞对EGFR酪氨酸激酶抑制剂(TKIs)敏感。长期的癌症治疗可能会导致对EGFR TKIs的获得性耐药。长非编码RNAs(Long Non-Coding RNAs，LncRNAs)在肺癌的肿瘤形成、转移和EGFR-TKI耐药的发生发展中起重要作用。为了深入了解EGFR-TKI耐药的分子机制，我们建立了一个耐EGFR-TKI的HCC827-8-1细胞株，并用lncRNA芯片分析了其表达模式，并与其亲本HCC827细胞株进行了比较。在HCC827-8-1细胞中，共有1,476个lncRNA转录本和1,026个信使核糖核酸转录本表达异常。用实时荧光定量聚合酶链式反应(Real-Time Quantity PCR)验证了筛选出的7个LncRNAs的表达水平。功能分析表明，几组lncRNAs可能通过其蛋白编码基因的顺式和/或反式调节参与了与EGFR-TKI抗性相关的生物通路。因此，lncRNAs可能成为未来EGFR-TKI治疗的新的候选生物标志物和潜在靶点。
Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827-8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis- and/or trans-regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.