Loss of Brain-enriched miR-124 MicroRNA Enhances Stem-like Traits and Invasiveness of Glioma Cells
ABSTRACT miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133(+) cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2.
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- "miR-124 is a miRNA enriched in the brain and plays a crucial role in gastrulation and neural development , . In addition, the expression of miR-124 was suppressed in several types of cancer, including medulloblastoma, glioma, oral squamous cell carcinomas and hepatocellular carcinoma –. Interestingly, its expression was down-regulated in breast cancer specimens and cell lines, and enforced expression of miR-124 showed a reduction in cell motility and invasion in human breast cancer cells . Over expression of miR-124 was linked to the suppression of inhibitory member of apoptosis-stimulating protein of p53 (iASPP), which subsequently led to an increased expression of NF-κB (p65) , . "
ABSTRACT: The emerging roles of microRNAs (miRNAs) and pulmonary epithelial cells in regulating the immune response against microbial invasion has attracted increasing attention in recent years, however, the immunoregulatory roles of miRNAs in the pulmonary epithelial cells in response to mycobacterial infection has not been fully demonstrated. In this study, we show that miR-124 expression is induced upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection in A549 alveolar epithelial cells and murine lungs. miR-124 is able to modulate Toll-like receptor (TLR) signaling in A459 cells. In this regard, multiple components, including TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α of the TLR signaling cascade are directly regulated by miR-124 in response to BCG stimulation. In addition, miR-124 expression was induced upon MyD88 overexpression and/or BCG stimulation, while silencing MyD88 expression by small interfering RNA dramatically down-regulated miR-124 transcription in A549 cells. These results indicate an underlying negative feedback mechanism between miR-124 and MyD88 in alveolar epithelial cells to prevent an excessive inflammatory response during mycobacterial infection. These observations suggest that miR-124 is a potential target for preventive and therapeutic intervention against the pulmonary tuberculosis, an infectious disease caused by Mycobacterium tuberculosis infection.PLoS ONE 04/2014; 9(4):e92419. DOI:10.1371/journal.pone.0092419 · 3.23 Impact Factor
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- "Overexpression of miR-124 has consistently been found to inhibit the CD133+ cell subpopulation of the neurosphere and to downregulate stem cell markers, such as BMI1, Nanog, and Nestin. These effects could be rescued by re-expression of SNAI2, another direct target of miR-124 (Xia et al., 2012). "
ABSTRACT: Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. Differentiation of GSCs may be regulated by multi-tiered epigenetic mechanisms that orchestrate the expression of thousands of genes. One such regulatory mechanism involves functional non-coding RNAs (ncRNAs), such as microRNAs (miRNAs); a large number of ncRNAs have been identified and shown to regulate the expression of genes associated with cell differentiation programs. Given the roles of miRNAs in cell differentiation, it is possible they are involved in the regulation of gene expression networks in GSCs that are important for the maintenance of the pluripotent state and for directing differentiation. Here, we review recent findings on ncRNAs associated with GSC differentiation and discuss how these ncRNAs contribute to the establishment of tissue heterogeneity during glioblastoma tumor formation.Frontiers in Genetics 02/2014; 5:14. DOI:10.3389/fgene.2014.00014
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- "A glioma study indicated that miR-124 is downregulated in both glioma tissues and cell lines. Through an integrated bioinformatics analysis and experimental confirmation, Xia et al34 identified SNAI2 as a potential direct target of miR-124, thereby restricting stem-like properties. In a study of pancreatic cancer, Wang et al35 reported that miR-124 is silenced by hypermethylation in tumor tissues and that miR-124 inhibits cell proliferation, invasion, and metastasis by targeting Rac 1 and inactivating the MKK4-JNK-c-Jun pathway. "
ABSTRACT: miRNAs (miRs) are short RNA molecules that are involved in the posttranscriptional regulation of mRNA. The roles of miRs in tumor pathogenesis have only recently become a focus of research. It is becoming increasingly clear that miRs are important regulators of apoptosis, proliferation, invasion, and metastasis in cancer cells during cancer genesis and progression, furthering our understanding of cancer. In the present review, we summarize and evaluate the recent advances in our understanding of the characteristics of miRs as well as their regulated functions in cancer stem cells (CSCs), the epithelial-mesenchymal transition (EMT), and the tumor microenvironment (TM), describing their roles in tumor pathogenesis and their possible use as new therapeutic targets and biomarkers.OncoTargets and Therapy 11/2013; 6:1675-1684. DOI:10.2147/OTT.S52730 · 2.31 Impact Factor