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BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths world-wide. Detection of molecular markers in stool samples is a promising strategy for CRC screening. MicroRNAs (miRNAs) are short, non-coding RNA molecules that are commonly dysregulated in neoplasia.OBJECTIVE: The objective of this study was to evaluate the fecal miRNAs differentiation between early-stage CRC patients and healthy subjects.METHODS: Stool samples were collected from 40 patients with early stage (I, II) CRC and 16 healthy controls. RNA was extracted from all samples using miRNAeasy Mini Kits. MiRNA microarray expression profiling was performed with Agilent's miRNA Microarray system on 12 CRC and 8 normal stool samples. The expression levels of miR-4478 and miR-1295b-3p were determined by the SYBR Green miScript PCR system. RESULTS: In profiling study, we found 215 down-regulated miRNAs in CRC group. Furthermore, in validation study we found that the expression levels of fecal miR-4487 and miR-1295b-3p were significantly decreased in CRC patients compared to healthy controls.CONCLUSIONS: The expression of miR-4478 and miR-1295b-3p were significantly diminished in stool samples of CRC patients with early stage (I, II) in comparison with normal group. These miRNAs maybe use as potential non-invasive molecular markers for CRC diagnosis, but further studies are needed. [ABSTRACT FROM AUTHOR]

The article discusses the use of microRNA microarray profiling as a biomarker tool in pediatric acute lymphoblastic leukemia (ALL). Noted is the conduct of unsupervised clustering to assess the correlation of microRNA expression with event-free survival and overall survival. The study also demonstrates the significance of microRNA for pediatric ALL relapse, progression, and survival.

Anti-EGFR monoclonal antibodies (anti-EGFRmAb) serve in the treatment of metastatic colorectal cancer (mCRC), but patients with a mutation in KRAS/BRAF and nearly one-half of those without the mutation fail to respond. We performed microRNA (miRNA) analysis to find miRNAs predicting anti-EGFRmAb efficacy. Of the 99 mCRC patients, we studied differential miRNA expression by microarrays from primary tumors of 33 patients who had wild-type KRAS/BRAF and third- to sixth-line anti-EGFRmAb treatment, with/without irinotecan. We tested the association of each miRNA with overall survival (OS) by the Cox proportional hazards regression model. Significant miR-31* up-regulation and miR-592 down-regulation appeared in progressive disease versus disease control. miR-31* expression and down-regulation of its target genes SLC26A3 and ATN1 were verified by quantitative reverse transcriptase polymerase chain reaction. Clustering of patients based on miRNA expression revealed a significant difference in OS between patient clusters. Members of the let-7 family showed significant up-regulation in the patient cluster with poor OS. Additionally, miR-140-5p up-regulation and miR-1224-5p down-regulation were significantly associated with poor OS in both cluster analysis and the Cox proportional hazards regression model. In mCRC patients with wild-type KRAS/BRAF, miRNA profiling can efficiently predict the benefits of anti-EGFRmAb treatment. Larger series of patients are necessary for application of these miRNAs as predictive/prognostic markers. [ABSTRACT FROM AUTHOR]

The association of microRNA alterations with progression and treatment outcome has been revealed in different types of cancers. To find miRNAs involved in imatinib response we performed miRNA microarray followed by RT-qPCR verification of 9 available diagnostic bone marrow core biopsies from 9 CML patients including 4 imatinib-resistant and 5 imatinib-responder patients. Only one differentially expressed miRNA, miR-181c, was found when the imatinib-resistant group was compared with imatinib-responders. Significant down-regulation of miR-181c in imatinib-resistant versus imatinib-responders was confirmed by qRT-PCR. Some miR-181c target genes such as PBX3, HSP90B1, NMT2 and RAD21 have been associated with drug response. [ABSTRACT FROM AUTHOR]

Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteins and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro , the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15. [ABSTRACT FROM AUTHOR]