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Glioblastoma multiforme (GBM), a World Health Organization grade IV glioma, is the most common and aggressive primary brain tumor in humans. microRNAs (miRNAs) are aberrantly expressed in numerous cancer types, including GBM. Abnormally expressed miRNAs are commonly associated with malignant characteristics of GBM, including malignant growth, proliferation, apoptosis, invasion, metastasis and resistance to chemotherapy. miRNA (miR)-376a is abnormally expressed in multiple human cancers; however, the expression pattern and role of miR-376a in GBM, and the underlying molecular mechanisms by which miR-376a exerts its functions remain to be elucidated. Therefore, the aim of this study was to measure miR-376a expression and determine its biological roles in GBM as well as its associated molecular mechanism. In the present study, miR-376a expression was markedly downregulated in GBM tissues and cell lines. Overexpression of miR-376a markedly decreased the proliferation and invasion of GBM cells in vitro. In the present study, specificity protein 1 (SP1) was demonstrated to be a direct target of miR-376a. In addition, a negative association between SP1 mRNA and miR-376a expression was observed in GBM tissues. SP1 upregulation reduced the effects of miR-376a overexpression on GBM cell proliferation and invasion. miR-376a may be a therapeutic target for the treatment of patients with GBM. [ABSTRACT FROM AUTHOR]

Depression is a serious and potentially life-threatening mental disorder with unknown etiology. Emerging evidence shows that brain-derived neurotrophic factor (BDNF) and microRNAs (miRNAs) play critical roles in the etiology of depression. However, the molecular mechanisms are not fully understood. Expression of miR-182 and BDNF in the hippocampus were analyzed in a chronic unpredictable mild stress (CUMS) model. Male Wistar rats received bilateral intra-hippocampal infusions of BDNF- and miR-182-expressing (miR-182) or miR-182-silencers (si-miR-182) lentiviral vectors (LV). miR-182 upregulation was correlated with decreased BDNF expression in the hippocampus of a CUMS model. Accordingly, an anti-depressant like effect was observed when LV-BDNF or LV-si-miR-182 was injected into the hippocampus. Moreover, BDNF and its target gene cyclic AMP responsive element binding protein 1 (CREB1) decreased following LV-miR-182 injection and increased upon LV-si-miR-182 injection in rat hippocampus and cultured neuronal cells. In contrast, miR-182 overexpression exacerbated depression-like behaviors and decreased BDNF. Further, luciferase reporter evidence confirmed BDNF was a miR-182 target. Taken together, the current results reveal a potential molecular regulation of miR-182 on BDNF and the pronounced behavioral consequences of this regulation. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression. [Copyright &y& Elsevier]

Abstract: MicroRNAs (miRNA) have emerged as key players in carcinogenesis. Here, we investigated the role of miR-137 in the pathogenesis of lung cancer. The downregulation of miR-137 in lung cancer cells could be rescued following inhibition of DNA methylation. Ectopic expression of miR-137 in lung cancer cells significantly downregulated Cdc42, Cdk6 and induced G1 cell cycle arrest, leading to a significant decrease in cell growth in vivo and in vitro. Further, both Cdc42 and Cdk6 were confirmed as targets of miR-137. [Copyright &y& Elsevier]

The aims of this study were to examine the levels of serum and exosomal miR-137, miR-155 and miR-223, three neuroinflammation-related miRNAs, in dementia patients and to explore the value of these miRNAs for the diagnosis and prognostic evaluation of dementia. Thirty-two patients with dementia were enrolled, and sixteen volunteers without dementia served as controls. Serum exosomes were isolated by precipitation with ExoQuick and characterized by western blotting, nanoparticle-tracking analysis and immunofluorescence microscopy. The levels of both total serum miRNAs and serum exosomal miRNAs were determined by real-time quantitative PCR. Total serum miRNAs and serum exosomal miRNAs were both detected to be down-regulated. The median level of serum exosomal miR-223 was significantly decreased in dementia patients ( p  < 0.01). The level of miR-223 was significantly correlated with Mini-Mental State Examination (MMSE) scores, Clinical Dementia Rating (CDR) scores, magnetic resonance spectroscopy (MRS) spectral ratios and serum concentrations of IL-1β, IL-6, TNF-α, and CRP. The diagnostic utility of exosomal miR-233 was evaluated by the area under the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was 0.875. This study suggests that serum exosomal miR-223 is a promising biomarker for diagnosing dementia and evaluating the progression of disease. [ABSTRACT FROM AUTHOR]