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      Ladinin-1 in actin arcs of oral squamous cell carcinoma is involved in cell migration and epithelial phenotype

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          Abstract

          Histopathologically, oral squamous cell carcinoma (OSCC) consists of well-defined interfaces with adjacent non-cancerous epithelium. Previously, we found that SCC tissues expressed higher levels of specific proteins at this interface. Ladinin-1 (LAD1) is one of the specific molecules that has increased expressions in cancer fronts; however, its function in OSCC is unknown. Therefore, this study aimed to elucidate the function of LAD1 in human OSCC cells. LAD1 was localized on the actin arc at the distal periphery of cell clusters in the OSCC cell lines HSC-2, HSC-3, and HSC-4. When LAD1 was knocked down, cellular migration was repressed in wound scratch assays but was reversed in three-dimensional collagen gel invasion assays. Characteristic LAD1 localization along actin arcs forming the leading edge of migrating cells was diminished with loss of filopodia formation and ruffling in knockdown cells, in which the expression levels of cell motility-related genes—p21-activated kinase 1 ( PAK1) and caveolin-1 ( CAV1)—were upregulated and downregulated, respectively. LAD1 expression was also associated with the downregulation of vimentin and increased histological differentiation of OSCC. These results suggest that LAD1 is involved in actin dynamics during filopodia and lamellipodia formation, and in maintaining the epithelial phenotype of OSCC cells.

          Supplementary Information

          The online version contains supplementary material available at 10.1038/s41598-024-74041-z.

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            STAR: ultrafast universal RNA-seq aligner.

            Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
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              The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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                Author and article information

                Contributors
                abet@dent.niigata-u.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 October 2024
                1 October 2024
                2024
                : 14
                : 22778
                Affiliations
                [1 ]Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, ( https://ror.org/04ww21r56) 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514 Japan
                [2 ]Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medicine, Niigata University, ( https://ror.org/04ww21r56) Niigata, Japan
                [3 ]Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, ( https://ror.org/04ww21r56) Niigata, Japan
                [4 ]Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, ( https://ror.org/04ww21r56) Niigata, Japan
                Article
                74041
                10.1038/s41598-024-74041-z
                11445451
                39354061
                4124d292-6714-4cb0-afd8-0468f360750e
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 22 October 2023
                : 23 September 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: 18K09550
                Award ID: 21K09841
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2024

                Uncategorized
                squamous cell carcinoma,ladinin-1,actin arc,cancer,oral cancer
                Uncategorized
                squamous cell carcinoma, ladinin-1, actin arc, cancer, oral cancer

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