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Comprehensive analysis of microRNAs in breast cancer

机译：乳腺癌中microRNA的综合分析

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Background MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in breast cancer progression by downregulating gene expression. The detailed mechanisms and biological functions of miRNA molecules in breast carcinogenesis have yet to be fully elucidated. This study used bioinformatics and experimental approaches to conduct detailed analysis of the dysregulated miRNAs, arm selection preferences, 3' end modifications, and position shifts in isoforms of miRNAs (isomiRs) in breast cancer. Methods Next-generation sequencing (NGS) data on breast cancer was obtained from the NCBI Sequence Read Archive (SRA). The miRNA expression profiles and isomiRs in normal breast and breast tumor tissues were determined by mapping the clean reads back to human miRNAs. Differences in miRNA expression and pre-miRNA 5p/3p arm usage between normal and breast tumor tissues were further investigated using stem-loop reverse transcription and real-time polymerase chain reaction. Results The analysis identified and confirmed the aberrant expression of 22 miRNAs in breast cancer. Results from pathway enrichment analysis further indicated that the aberrantly expressed miRNAs play important roles in breast carcinogenesis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Data also indicated that the position shifts in isomiRs and 3' end modifications were consistent in breast tumor and adjacent normal tissues, and that 5p/3p arm usage of some miRNAs displayed significant preferences in breast cancer. Conclusions Expression pattern and arm selection of miRNAs are significantly varied in breast cancers through analyzing NGS data and experimental approach. These miRNA candidates have high potential to play critical roles in the progression of breast cancer and could potentially provide as targets for future therapy.
机译：背景MicroRNA（miRNA）是短的非编码RNA（长度约为22个核苷酸），通过下调基因表达在乳腺癌的进展中发挥重要作用。 miRNA分子在乳腺癌致癌作用中的详细机制和生物学功能尚未完全阐明。这项研究使用生物信息学和实验方法对乳腺癌中失调的miRNA，臂选择偏好，3'末端修饰以及miRNA同工型（isomiRs）的位置变化进行了详细分析。方法从NCBI序列阅读档案（SRA）获得有关乳腺癌的下一代测序（NGS）数据。正常乳腺和乳腺肿瘤组织中的miRNA表达谱和isomiRs通过将干净的读数映射回人miRNA来确定。使用茎环逆转录和实时聚合酶链反应进一步研究了正常和乳腺肿瘤组织之间的miRNA表达和前miRNA 5p / 3p臂使用的差异。结果分析鉴定并证实了22种miRNA在乳腺癌中的异常表达。途径富集分析的结果进一步表明，异常表达的miRNA通过调节有丝分裂原激活的蛋白激酶（MAPK）信号传导途径在乳腺癌的发生中起重要作用。数据还表明，在乳腺肿瘤和邻近的正常组织中，isomiRs和3'末端修饰的位置一致，并且某些miRNA的5p / 3p臂使用显示出对乳腺癌的明显偏爱。结论通过分析NGS数据和实验方法，乳腺癌中miRNA的表达模式和臂选择存在显着差异。这些miRNA候选物在乳腺癌的进展中具有重要作用，并且有可能作为未来治疗的靶标。

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