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      MicroRNA‐451a acts as tumor suppressor in cutaneous basal cell carcinoma

      research-article
      1 , 1 ,
      Molecular Genetics & Genomic Medicine
      John Wiley and Sons Inc.
      Basal cell carcinoma, K5tTA/TREGLI1, miRNA‐451a, TBX1

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          Abstract

          Background

          Basal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA‐451a as a novel tumor suppressor in cutaneous BCC.

          Methods

          We first evaluated miRNA‐451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR‐451a in cell proliferation, colony formation potential, and cell cycle pattern. Next, we employed luciferase reporter assay and western blotting to evaluate TBX1 as a downstream target of miRNA‐451a. Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR.

          Results

          miRNA‐451a was significantly reduced in human BCC tissues. The downregulation of miRNA‐451a was also confirmed in BCC mouse model. Overexpressing miRNA‐451a in tumor cells markedly suppressed cell growth through G1 cell cycle arrest. However, inhibiting miRNA‐451a in primary cells promoted cell growth and colony formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA‐451a and this was confirmed by luciferase assay and protein expression. Finally, TBX1 level was shown upregulated in BCC tissues as inversely to miR451a.

          Conclusion

          Our studies revealed that miRNA‐451a/ TBX1 axis played a pivotal role in BCC tumorigenesis.

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          Most cited references20

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          Therapeutic targeting of microRNAs: current status and future challenges.

          MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.
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            Basal-cell carcinoma.

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              Basal cell carcinoma.

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                Author and article information

                Contributors
                jiangpingdongwx@126.com
                Journal
                Mol Genet Genomic Med
                Mol Genet Genomic Med
                10.1002/(ISSN)2324-9269
                MGG3
                Molecular Genetics & Genomic Medicine
                John Wiley and Sons Inc. (Hoboken )
                2324-9269
                13 September 2018
                November 2018
                : 6
                : 6 ( doiID: 10.1002/mgg3.2018.6.issue-6 )
                : 1001-1009
                Affiliations
                [ 1 ] Department of Dermatology Wuxi No.2 People’s Hospital Wuxi, Jiangsu China
                Author notes
                [*] [* ] Correspondence

                Pingdong Jiang, Department of Dermatology, Wuxi No.2 People’s Hospital, Wuxi, Jiangsu, China.

                Email: jiangpingdongwx@ 123456126.com

                Author information
                http://orcid.org/0000-0003-4862-419X
                Article
                MGG3473
                10.1002/mgg3.473
                6305666
                30209892
                56e8abd4-4d16-4415-a838-b9952fae3b6e
                © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 July 2018
                : 17 August 2018
                : 21 August 2018
                Page count
                Figures: 6, Tables: 0, Pages: 9, Words: 10139
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                mgg3473
                November 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.4 mode:remove_FC converted:25.12.2018

                basal cell carcinoma,k5tta/tregli1,mirna‐451a,tbx1
                basal cell carcinoma, k5tta/tregli1, mirna‐451a, tbx1

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