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Findings from multiple studies on microRNA (miRNA) expression profiling in schizophrenia patients have produced conflicting results. In order to investigate miRNA as specific biomarkers in the peripheral plasma and peripheral blood mononuclear cells (PBMC) of schizophrenia patients, expression levels of the nine most frequently reported schizophrenia-associated miRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) were examined in the peripheral plasma and PBMC in 25 schizophrenia patients and 13 healthy controls using quantitative real-time reverse transcription polymerase chain reaction. We observed significantly increased expressions of miR-132, miR-195, miR-30e and miR-7 in plasma samples ( p < 0.05 to p < 0.001), and miR-212, miR-34a and miR-30e in PBMC samples ( p < 0.05 to p < 0.01). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of miR-30e in plasma was 0.767 (95% confidence interval [CI] 0.608–0.926) with sensitivity and specificity of 90.90% and 60.00% respectively, and the AUC of miR-30e in PBMC was 0.756 (95% CI 0.584–0.929) with sensitivity and specificity of 81.80% and 68.00%, respectively. Logistic regression analysis demonstrated that miR-30e in plasma was more sensitive to differentiate schizophrenia patients from normal controls than miR-30e in PBMC. Our findings indicate that miRNA expression is more significant in plasma than in PBMC, and suggest that miR-30e in plasma may be a more sensitive biomarker for schizophrenia diagnosis, although its aberrant expression can be detected in both plasma and PBMC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with significantly high prevalence in Southern China. Unlike other head and neck cancers, mutations or deletions of tumor suppressor genes in NPC are not common. Recently, downregulation of tumor suppressor genes expression by microRNA (miRNA) is increasingly recognized as an important mechanism of nasopharyngeal tumorigenesis. In this study, we reported that microRNA-144 (miR-144) was frequently upregulated in NPC specimens and cell lines. Repression of miR-144 significantly decreased cell proliferation, clonogenicity, migration, invasion and tumor formation in nude mice, while restoring miR-144 in miR-144-attenuated NPC cells exhibited a strong tumorigenic role. Further, we found that miR-144 was inversely correlated with the tumor suppressor gene phosphatase and tensin homolog (PTEN) in NPC specimens and cell lines, and then we identified PTEN as a direct target of miR-144 in NPC cell lines. PTEN downregulation in miR-144-attenuated cells could increase cell growth, migration and invasion. Mechanistic investigations revealed that miR-144 suppressed the expression of PTEN to increase the expression of pAkt and cyclin D1 to promote G1-phase transition and decrease E-cadherin to promote migration and invasion. Taken together, we provide compelling evidence that miR-144 functions as an onco-miRNA in NPC, and its oncoeffects are mediated chiefly by repressing PTEN expression to activate the PI3K/Akt pathway. [ABSTRACT FROM PUBLISHER]

Schizophrenia is a severe and debilitating psychiatric disorder of unknown etiology, and its diagnosis is essentially based on clinical symptoms. Despite growing evidence on the relation of altered expression of miRNAs and schizophrenia, most patients with schizophrenia usually had an extensive antipsychotic treatment history before miRNA expression profile analysis, and the pharmacological effects on miRNA expression are largely unknown. To overcome these impediments, miRNA microarray analysis was performed in peripheral blood mononuclear cells (PBMCs) obtained from patients with schizophrenia who were not on antipsychotic medication and healthy controls. Then, using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we verified the top 10 miRNAs with the highest fold-change values from microarray analysis in 82 patients with schizophrenia and 43 healthy controls, and nine miRNAs demonstrated significant differences in expression levels. Finally, we compared these nine miRNA profiles before and after antipsychotic treatment. Our results revealed that serum miR-21 expression decreased strikingly in patients after antipsychotic treatment. The change of miR-21 expression was negatively correlated with improvement of positive, general psychopathology, and aggressiveness symptoms. This study preliminarily analyzed the possible changes in circulating miRNAs expression in response to antipsychotic medication for schizophrenia, and the molecular mechanisms of this needs to be further explored. [ABSTRACT FROM AUTHOR]

Currently, diagnosis and treatment of major depressive disorder (MDD) are based on the patients' description of symptoms, mental status examinations, and clinical behavioral observations, which increases the chance of misdiagnosis. There is a serious need to find a practical biomarker for the proper diagnosis of MDD. This study aimed to explore the possibility of microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) as specific blood-based biomarker for MDD patients. By using an Affymetrix array that covers 723 human miRNAs, we identified 26 miRNAs with significant changes in expression in PBMCs of MDD patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 81 MDD patients and 46 healthy controls confirmed that the expression levels of 5 miRNAs (miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, and miRNA-4743) were up-regulated. By receiver operating characteristic (ROC) curve analysis, the combining area under the ROC curve (AUC) of these five miRNAs was 0.636 [95% confidence interval (CI): 0.58-0.90]. MiRNA target gene prediction and functional annotation analysis showed that there was a significant enrichment in several pathways associated with nervous system and brain functions, supporting the hypothesis that differentially-regulated miRNAs may be involved in mechanism underlying development of MDD. We conclude that altered expression of miRNAs in PMBCs might be involved in multiple stages of MDD pathogenesis, and thus might be able to serve as specific biomarker for diagnosis of MDD. [ABSTRACT FROM AUTHOR]

Abstract: Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses. [Copyright &y& Elsevier]