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.

MicroRNA-324 in Human Cancer: miR-324-5p and miR-324-3p Have Distinct Biological Functions in Human Cancer

“…However, we obtained interesting data showing significantly different arm selection preferences of miR-324 in human cancer tissues and the corresponding adjacent normal tissues ( Figure 1C). This finding is in concordance with our previous findings that arm selection preferences of some miRNAs varied in different tissues, developmental stages, species, and cancer types (7)(8)(9)(10)23).…”

“…In addition, miR-324-5p has been shown to suppress glioma and HCC cell growth (19,20). We previously reported that the selection preference of miR-324 for 5p and 3p arms significantly varied in breast cancer compared to that in adjacent normal tissues analyzed using next-generation sequencing data from the Sequence Read Archive database (8). However, the related biological functions of miR-324-5p and -3p require clarification in human cancer.…”

miRNA in Rat Liver Sinusoidal Endothelial Cells and Hepatocytes and Application to Circulating Biomarkers that Discern Pathogenesis of Liver Injuries

“…In rats, miR-511-3p is relatively abundant in isolated LSECs (Figure 2A) and the liver 9 compared with miR-511-5p, and is also abundant in humans, at least in breast cancer cells. 38 Thus, further studies on disease or injury specificity of plasma miR-511-3p are needed. ajp.amjpathol.org -The American Journal of Pathology In summary, we provided miRNA expression profiles in the isolated hepatocytes and LSECs from rats and identified LSEC-specific miRNAs by considering organ specificity.…”

Next-generation Sequencing for microRNA Profiling: MicroRNA-21-3p Promotes Oral Cancer Metastasis

“…Although, miR-21-3p and -5p are generated from the same precursor (pre-miR-21), the role and biological function of the passenger strand, miR-21-3p, in OSCC remains unclear. Moreover, studies have indicated that the expression of miR#-5p and -3p arms is frequently coexpressed and coordinately regulated in human cancers (22)(23)(24). Therefore, the expression preference of the -5p and -3p arms of most miRNAs is consistent in human cancers; only a few of the miR-#-5p and -3p arms can be preferentially selected during cancer progression, which suggests that they might have a distinct biological function in human cancers (23)(24)(25)(26).…”