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Purpose: MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis. Patients and methods: MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study. Results: After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity. Conclusions: The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) have become reliable sources of non‐invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). Methods: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan‐Meier curves using log‐rank tests. Results: We identified a 7‐miRNA signature including let‐7b‐5p, miR‐140‐3p, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, miR‐20b‐5p, and miR‐205‐5p in plasma for NPC diagnosis after four‐stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, and miR‐205‐5p were consistently up‐regulated while let‐7b‐5p and miR‐140‐3p were significantly down‐regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma‐derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. Conclusion: We identified a 7‐miRNA signature in plasma as promising non‐invasive biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection. Highlights • We investigated plasma miRNA profiles of CRC in a four-stage process and present a seven-miRNA signature in discriminating CRC. • We found that miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were significantly up-regulated in CRC tissues. • We found that miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. • We discovered that plasma miR-26a-5p was only up-regulated in colon cancer patients but not in rectal cancer. • We found none of the seven miRNAs demonstrated significant different expression in patients with stage III + IV compared to those with stage I + II. • We found that no difference of the above seven plasma miRNA between left-sided and right-sided CRC. [ABSTRACT FROM AUTHOR]

We looked for differentially expressed MicroRNAs (miRNAs) in Immunoglobulin A nephropathy (IgAN). Forty-eight miRNAs were identified through the initial screening phase (2 IgAN pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V 1 .M). By qRT-PCR, these miRNAs were further assessed in the training (32 IgAN VS. 31 NCs) and testing stages (51 IgAN VS. 51 NCs). The renal pathological lesions of patients with IgAN were evaluated according to Lee's grading system. We discovered a plasma miRNA signature including four up-regulated miRNAs (miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p) and the areas under the receiver operating characteristic (ROC) curve (AUC) were 0.80 and 0.76 for the training and testing stage, respectively. The expression of the four miRNAs in IgAN grade I–II subgroups (according to Lee's grading system) was obviously higher than that in IgAN grade III-V ( P  < .05). In summary, the plasma e xpression of miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p were up-regulated in patients with IgAN, especially the early-stage disease. Further studies are needed to explore the roles of the four miRNAs in the pathogenesis and progression of IgAN. [ABSTRACT FROM AUTHOR]

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b), and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC. [ABSTRACT FROM AUTHOR]