Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing

Molecular Cancer

Research

Yung-Hua Lee¹  Yao-Yin Chang²  Jui-Hui Hung³  Chien-Yueh Lee³  Eric Y Chuang³  Fon-Jou Hsieh⁴  Liang-Chuan Lai⁵  Chiun-Sheng Huang⁶  Wen-Hung Kuo⁶  King-Jen Chang⁷  Mong-Hsun Tsai⁸  Wen-Chun Lin⁸  Cheng-Ying Shen⁸  Ya-Chu Chang⁸ 

[1] Bioinformatics and Biostatistics Core, NTU Center of Genomic Medicine, Taipei, Taiwan;Department of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan;Department of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan;Bioinformatics and Biostatistics Core, NTU Center of Genomic Medicine, Taipei, Taiwan;Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Surgery, Cheng Ching General Hospital, Taichung, Taiwan;Institute of Biotechnology, College of Bio-resources and Agriculture, National Taiwan University, Taipei, Taiwan;

关键词: Triple-negative breast cancer;    Deep sequencing;    MicroRNA expression;    MicroRNA cluster;    miR-130b-5p;    CCNG2;   

DOI  :  10.1186/s12943-015-0301-9

 received in 2014-06-16, accepted in 2015-01-21,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are short, non-coding RNA molecules that play critical roles in human malignancy. However, the regulatory characteristics of miRNAs in triple-negative breast cancer, a phenotype of breast cancer that does not express the genes for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, are still poorly understood.MethodsIn this study, miRNA expression profiles of 24 triple-negative breast cancers and 14 adjacent normal tissues were analyzed using deep sequencing technology. Expression levels of miRNA reads were normalized with the quantile-quantile scaling method. Deregulated miRNAs in triple-negative breast cancer were identified from the sequencing data using the Student’s t-test. Quantitative reverse transcription PCR validations were carried out to examine miRNA expression levels. Potential target candidates of a miRNA were predicted using published target prediction algorithms. Luciferase reporter assay experiments were performed to verify a putative miRNA-target relationship. Validated molecular targets of the deregulated miRNAs were retrieved from curated databases and their associations with cancer progression were discussed.ResultsA novel 25-miRNA expression signature was found to effectively distinguish triple-negative breast cancers from surrounding normal tissues in a hierarchical clustering analysis. We documented the evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNAs in triple-negative breast cancer. Two of these miRNA clusters (miR-143-145 at 5q32 and miR-497-195 at 17p13.1) were markedly down-regulated in triple-negative breast cancer, while the other five miRNA clusters (miR-17-92 at 13q31.3, miR-183-182 at 7q32.2, miR-200-429 at 1p36.33, miR-301b-130b at 22q11.21, and miR-532-502 at Xp11.23) were up-regulated in triple-negative breast cancer. Moreover, miR-130b-5p from the miR-301b-130b cluster was shown to directly repress the cyclin G2 (CCNG2) gene, a crucial cell cycle regulator, in triple-negative breast cancer cells. Luciferase reporter assays showed that miR-130b-5p-mediated repression of CCNG2 was dependent on the sequence of the 3′-untranslated region. The findings described in this study implicate a miR-130b-5p-CCNG2 axis that may be involved in the malignant progression of triple-negative breast cancer.ConclusionsOur work delivers a clear picture of the global miRNA regulatory characteristics in triple-negative breast cancer and extends the current knowledge of microRNA regulatory network.

【 授权许可】

CC BY   
© Chang et al.; licensee Biomed Central. 2015