Li Guo, Qiu Yuanzheng, Su Zhongwu, Ren Shuling, Liu Chao, Tian Yongquan, Liu Yong
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, China ; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China.
PLoS One. 2013 Dec 19;8(12):e84486. doi: 10.1371/journal.pone.0084486. eCollection 2013.
Rapidly growing evidence suggests that microRNAs (miRNAs) are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC.
The differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models.
50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501), 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323) and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1) and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1).
Our study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance.
越来越多的证据表明，微小RNA（miRNA）参与了包括放射抗性在内的多种癌症恶性行为。因此，本研究旨在调查与鼻咽癌放射抗性相关的miRNA表达模式。
构建了与鼻咽癌放射抗性相关的miRNA和mRNA差异表达谱。通过生物信息学算法分析了miRNA的预测靶mRNA及其富集的信号通路。最后，在两种鼻咽癌放射抗性细胞模型中验证了部分miRNA和与通路相关的靶mRNA。
鉴定出50个已知和9个新的具有显著差异的miRNA，其靶mRNA被缩小到53个鼻咽癌特异性mRNA。随后的KEGG分析表明，这53个mRNA在37条信号通路中富集。进一步的qRT-PCR分析证实了3个下调的miRNA（miR-324-3p、miR-93-3p和miR-4501）、3个上调的miRNA（miR-371a-5p、miR-34c-5p和miR-1323）以及2个新的miRNA。此外，还观察到与通路相关的靶mRNA的相应变化，包括5个上调的mRNA（ICAM1、WNT2B、MYC、HLA-F和TGF-β1）和3个下调的mRNA（CDH1、PTENP1和HSP90AA1）。
我们的研究提供了miRNA表达谱及其与靶mRNA之间相互作用的概述，这将加深我们对miRNA在鼻咽癌放射抗性中重要作用的理解。
