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MicroRNAs (miRNAs) regulate multiple transcripts and thus shape the expression landscape of a cell. Information about miRNA expression and distribution across cell types is crucial for the understanding of miRNAs’ functions and their translational applications as biomarkers or therapeutic targets. In this study, we identify cell-type-specific miRNAs by combining multiple correspondence analysis and Gini coefficients to dissect miRNAs’ expression profiles and chromatin activity score profiles, which results in collections of chromatin activity-specific miRNAs in 91 cell types and expression-specific miRNAs in 124 cell types. Moreover, we find that cell-type-specific miRNAs are closely associated with disease miRNAs, such as T-cell-specific miRNAs, which are closely associated with cancer prognosis. Finally, we constructed mirCellType, an online tool based on cell-type-specific miRNA signatures, to dissect the cell type composition of complex samples with miRNA expression profiles.

Background Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs. Methods The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms. Results After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant. Conclusions The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data. There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

Background This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients. Methods Baseline PBMC samples from eight responders and eight non‐responders after 24‐week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24‐week TNF inhibitor (etanercept). Responders and non‐responders were divided referring to the decline in disease activity score in 28 joints. Results In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non‐responders, which were mainly enriched in regulating immune‐ and inflammation‐related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR‐192‐5p, miR‐146a‐5p, miR‐19b‐3p, miR‐320c, miR‐335‐5p, miR‐149‐3p, miR‐766‐3p, let‐7a‐5p, miR‐24‐3p, and miR‐1226‐5p. In qPCR validation, miR‐146a‐5p was increased, while let‐7a‐5p was decreased in responders compared with non‐responders. Multivariate logistic analysis illuminated that miR‐146a‐5p and CRP independently correlated with higher clinical response, while let‐7a‐5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781‐0.945. Conclusion miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR‐146a‐5p, let‐7a‐5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients.

Background Although more than 246 loci/genes are associated with inherited retinal diseases, the mechanistic events that link genetic mutations to photoreceptor cell death are poorly understood. miRNAs play a relevant role during retinal development and disease. Thus, as a first step in characterizing miRNA involvement during disease expression and progression, we examined miRNAs expression changes in normal retinal development and in four canine models of retinal degenerative disease. Results The initial microarray analysis showed that 50 miRNAs were differentially expressed (DE) early (3 vs. 7 wks) in normal retina development, while only 2 were DE between 7 and 16 wks, when the dog retina is fully mature. miRNA expression profiles were similar between dogs affected with xlpra2, an early-onset retinal disease caused by a microdeletion in RPGRORF15, and normal dogs early in development (3 wks) and at the peak of photoreceptor death (7 wks), when only 2 miRNAs were DE. However, the expression varied much more markedly during the chronic cell death stage at 16 wks (118 up-/55 down-regulated miRNAs). Functional analyses indicated that these DE miRNAs are associated with an increased inflammatory response, as well as cell death/survival. qRT-PCR of selected apoptosis-related miRNAs (“apoptomirs”) confirmed the microarray results in xlpra2, and extended the analysis to the early-onset retinal diseases rcd1 (PDE6B-mutation) and erd (STK38L-mutation), as well as the slowly progressing prcd (PRCD-mutation). The results showed up-regulation of anti-apoptotic (miR-9, -19a, -20, -21, -29b, -146a, -155, -221) and down-regulation of pro-apoptotic (miR-122, -129) apoptomirs in the early-onset diseases and, with few exceptions, also in the prcd-mutants. Conclusions Our results suggest that apoptomirs might be expressed by diseased retinas in an attempt to counteract the degenerative process. The pattern of expression in diseased retinas mirrored the morphology and cell death kinetics previously described for these diseases. This study suggests that common miRNA regulatory mechanisms may be involved in retinal degeneration processes and provides attractive opportunities for the development of novel miRNA-based therapies to delay the progression of the degenerative process. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-172) contains supplementary material, which is available to authorized users.