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      LIN28 Expression in Rat Spinal Cord After Injury

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          Abstract

          LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. However, its expression and function in central nervous system still unclear. In this study, we performed an acute spinal cord contusion injury (SCI) model in adult rats and investigated the dynamic changes of LIN28 expression in spinal cord. Western blot and immunohistochemistry analysis revealed that LIN28 was present in normal spinal cord. It gradually increased, reached a peak at 3 day, and then nearly declined to the basal level at 14 days after SCI. Double immunofluorescence staining showed that LIN28 immunoreactivity was found in neurons, astrocytes and a handful of microglia. Interestingly, LIN28 expression was increased predominantly in astrocytes but not in neurons. Moreover, the colocalization of LIN28 and proliferating cell nuclear antigen was detected after injury. Western blot showed that LIN28 participated in lipopolysaccharide (LPS) induced astrocytes inflammatory responses by NF-κB signaling pathway. These results suggested that LIN28 may be involved in the pathologic process of SCI, and further research is needed to have a good understanding of its function and mechanism.

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            The Lin28/let-7 axis regulates glucose metabolism.

            The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Lin28 Enhances Tumorigenesis and is Associated With Advanced Human Malignancies

              Multiple members of the let-7 family of miRNAs are often repressed in human cancers1,2, thereby promoting oncogenesis by de-repressing the targets K-Ras, c-Myc, and HMGA2 3,4. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins Lin28 and Lin28B block let-7 precursors from being processed to mature miRNAs5–8, suggesting that over-expression of Lin28/Lin28B might promote malignancy via repression of let-7. Here we show that LIN28 and LIN28B are over-expressed in primary human tumors and human cancer cell lines (overall frequency ∼15%), and that over-expression is linked to repression of let-7 family miRNAs and de-repression of let-7 targets. Lin28/Lin28B facilitate cellular transformation in vitro, and over-expression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28/LIN28B with poor clinical prognosis.
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                Author and article information

                Contributors
                nttaotao@ntu.edu.cn
                yueying1500628@163.com , guxingxing@ntu.edu.cn
                Journal
                Neurochem Res
                Neurochem. Res
                Neurochemical Research
                Springer US (Boston )
                0364-3190
                1573-6903
                4 April 2014
                4 April 2014
                2014
                : 39
                : 862-874
                Affiliations
                [ ]The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001 People’s Republic of China
                [ ]Department of Pathogen Biology, Medical School, Nantong University, Nantong, 226001 People’s Republic of China
                [ ]Basic Medial Research Center, Medical School, Nantong University, Nantong, 226001 People’s Republic of China
                [ ]Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001 People’s Republic of China
                [ ]Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001 People’s Republic of China
                [ ]Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433 People’s Republic of China
                Article
                1278
                10.1007/s11064-014-1278-2
                4000414
                24700281
                be1030c2-1a16-4b51-8d6e-0a63a64cb619
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 19 November 2013
                : 19 February 2014
                : 11 March 2014
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media New York 2014

                Neurosciences
                lin28,spinal cord injury,inflammatory,astrocytes
                Neurosciences
                lin28, spinal cord injury, inflammatory, astrocytes

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