Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing

Guo Li; Yuanzheng Qiu; Zhongwu Su; Shuling Ren; Chao Liu; Yongquan Tian; Yong Liu

doi:10.1371/journal.pone.0084486

Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing

PLoS One. 2013 Dec 19;8(12):e84486. doi: 10.1371/journal.pone.0084486. eCollection 2013.

Authors

Guo Li¹, Yuanzheng Qiu¹, Zhongwu Su¹, Shuling Ren¹, Chao Liu¹, Yongquan Tian¹, Yong Liu¹

Affiliation

¹ 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.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Carcinoma
Cell Line, Tumor
Gene Expression Profiling
Gene Regulatory Networks
Genomics*
High-Throughput Nucleotide Sequencing*
Humans
MicroRNAs / genetics*
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / genetics*
Nasopharyngeal Neoplasms / pathology*
Radiation Tolerance / genetics*
Sequence Analysis, RNA*

Substances

MicroRNAs

Grants and funding

Grants were provided by the National Natural Science Foundation of China (No. 81202128 and No.81272974), the Research Fund for the Doctoral Program of Higher Education of China (No.20120162120049), and the Freedom Explore Program of Central South University (No. 2012QNZT099). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.