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      A comprehensive analysis of coding and non-coding transcriptomic changes in cutaneous squamous cell carcinoma

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          Abstract

          Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression. To identify mRNAs, lncRNAs and circRNAs, which can be involved in cSCC, RNA-seq was performed on nine cSCCs and seven healthy skin samples. Representative transcripts were validated by NanoString nCounter assays using an extended cohort, which also included samples from pre-cancerous skin lesions (actinic keratosis). 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs were identified to be differentially expressed in cSCC. Targets of 519 transcription factors were enriched among differentially expressed genes, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were were identified to be dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel skin-enriched circRNAs, circ_IFFO2 and circ_POF1B, were identified and validated. In conclusion, a reference set of coding and non-coding transcripts were identified in cSCC, which may become potential therapeutic targets or biomarkers.

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          Most cited references35

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          Chemokines in cancer.

          Chemokines are chemotactic cytokines that control the migration of cells between tissues and the positioning and interactions of cells within tissue. The chemokine superfamily consists of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane spanning signaling receptors. Chemokines mediate the host response to cancer by directing the trafficking of leukocytes into the tumor microenvironment. This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and protumor activities. Although chemokines were initially appreciated as important mediators of immune cell migration, we now know that they also play important roles in the biology of nonimmune cells important for tumor growth and progression. Chemokines can directly modulate the growth of tumors by inducing the proliferation of cancer cells and preventing their apoptosis. They also direct tumor cell movement required for metastasis. Chemokines can also indirectly modulate tumor growth through their effects on tumor stromal cells and by inducing the release of growth and angiogenic factors from cells in the tumor microenvironment. In this Masters of Immunology primer, we focus on recent advances in understanding the complex nature of the chemokine system in tumor biology with a focus on how the chemokine system could be used to augment cancer immunotherapeutic strategies to elicit a more robust and long-lasting host antitumor immune response.
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            Cutaneous squamous cell carcinoma

            Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs are successfully eradicated by surgical excision, a subset of cSCC possesses features associated with a higher likelihood of recurrence, metastasis, and death. The proper identification of these aggressive cSCCs can guide additional work-up and management. In the first article in this continuing medical education series, we discuss the incidence, recurrence rates, mortality rates, and risk factors associated with cSCC and review the staging systems used to stratify patients into high- and low-risk groups. The second article in this series reviews the treatment options for cSCC, with focused attention on the management of high-stage tumors.
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              Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes.

              Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different species and tissues. However, there is no global view of tissue specificity for circRNAs to date. Here we performed the comprehensive analysis to characterize the features of human and mouse tissue-specific (TS) circRNAs. We identified in total 302 853 TS circRNAs in the human and mouse genome, and showed that the brain has the highest abundance of TS circRNAs. We further confirmed the existence of circRNAs by reverse transcription polymerase chain reaction (RT-PCR). We also characterized the genomic location and conservation of these TS circRNAs and showed that the majority of TS circRNAs are generated from exonic regions. To further understand the potential functions of TS circRNAs, we identified microRNAs and RNA binding protein, which might bind to TS circRNAs. This process suggested their involvement in development and organ differentiation. Finally, we constructed an integrated database TSCD (Tissue-Specific CircRNA Database: http://gb.whu.edu.cn/TSCD) to deposit the features of TS circRNAs. This study is the first comprehensive view of TS circRNAs in human and mouse, which shed light on circRNA functions in organ development and disorders.
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                Author and article information

                Contributors
                andor.pivarcsi@ki.se
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                27 February 2020
                27 February 2020
                2020
                : 10
                : 3637
                Affiliations
                [1 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Dermatology and Venereology Division, Department of Medicine Solna, , Karolinska Institutet, ; Stockholm, Sweden
                [2 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Center for Molecular Medicine, , Karolinska Institutet, ; Stockholm, Sweden
                [3 ]GRID grid.452834.c, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, , Science for Life Laboratory, ; SE-171 77 Stockholm, Sweden
                [4 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Unit of Dermatology, , Karolinska University Hospital, ; SE-17176 Stockholm, Sweden
                [5 ]ISNI 0000 0001 1016 9625, GRID grid.9008.1, Department of Dermatology and Allergology, Faculty of Medicine, , University of Szeged, ; Szeged, Hungary
                [6 ]ISNI 0000 0000 8922 7789, GRID grid.14778.3d, Department of Dermatology, , University Hospital Düsseldorf, ; Düsseldorf, Germany
                [7 ]ISNI 0000 0001 1956 2722, GRID grid.7048.b, Interdisciplinary Nanoscience Center (iNANO), , Aarhus University, ; DK-8000 Aarhus, Denmark
                [8 ]ISNI 0000 0001 1956 2722, GRID grid.7048.b, Department of Molecular Biology and Genetics, , Aarhus University, ; Aarhus, Denmark
                [9 ]ISNI 0000 0001 1016 9625, GRID grid.9008.1, Research Institute of Translational Biomedicine, , University of Szeged, ; Szeged, Hungary
                Author information
                http://orcid.org/0000-0002-4438-6756
                http://orcid.org/0000-0002-2119-9501
                http://orcid.org/0000-0002-5980-7939
                http://orcid.org/0000-0003-2196-1102
                Article
                59660
                10.1038/s41598-020-59660-6
                7046790
                32108138
                bdffa360-15fb-4656-ab6a-f5a96fa8ff0e
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 May 2019
                : 31 January 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004359, Vetenskapsrådet (Swedish Research Council);
                Award ID: Dnr. 2015-02844
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002794, Cancerfonden (Swedish Cancer Society);
                Award ID: CAN 2018/801
                Award ID: CAN 2015/694
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                squamous cell carcinoma,long non-coding rnas,transcriptomics
                Uncategorized
                squamous cell carcinoma, long non-coding rnas, transcriptomics

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