title: Comprehensive analysis of microRNAs in breast cancer.
abstract: 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.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Ho
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Pan
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
authors.forename: Ling-Yueh
authors.initials: LY
authors.lastname: Hu
authors.forename: Shou-Yu
authors.initials: SY
authors.lastname: Yu
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Li
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D035683:MicroRNAs; D020928:Mitogen-Activated Protein Kinases