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      MiR‐375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion

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          Abstract

          We aimed to detect the functions of miR‐375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR‐375 and SLC7A11 in OSCC tissues and cells were measured with RT‐qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR‐375 and SLC7A11 in CAL‐27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR‐375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR‐375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR‐375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR‐375 upregulated cells. Collective data suggested that miR‐375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR‐375 or knockout of SLC7A11 could be therapeutically exploited.

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          The microcosmos of cancer.

          The discovery of microRNAs (miRNAs) almost two decades ago established a new paradigm of gene regulation. During the past ten years these tiny non-coding RNAs have been linked to virtually all known physiological and pathological processes, including cancer. In the same way as certain key protein-coding genes, miRNAs can be deregulated in cancer, in which they can function as a group to mark differentiation states or individually as bona fide oncogenes or tumour suppressors. Importantly, miRNA biology can be harnessed experimentally to investigate cancer phenotypes or used therapeutically as a target for drugs or as the drug itself.
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            MicroRNA control of signal transduction.

            MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
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              Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins.

              Transport system xc- found in plasma membrane of cultured mammalian cells is an exchange agency for anionic amino acids with high specificity for anionic form of cystine and glutamate. We have isolated cDNA encoding the transporter for system xc- from mouse activated macrophages by expression in Xenopus oocytes. The expression of system xc- activity in oocytes required two cDNA transcripts, and the sequence analysis revealed that one is identical with the heavy chain of 4F2 cell surface antigen (4F2hc) and the other is a novel protein of 502 amino acids with 12 putative transmembrane domains. The latter protein, named xCT, showed a significant homology with those recently reported to mediate cationic or zwitterionic amino acid transport when co-expressed with 4F2hc. Thus xCT is a new member of a family of amino acid transporters that form heteromultimeric complex with 4F2hc, with a striking difference in substrate specificity. The expression of system xc- was highly regulated, and Northern blot analysis demonstrated that the expression of both 4F2hc and xCT was enhanced in macrophages stimulated by lipopolysaccharide or an electrophilic agent. However, the expression of xCT was more directly correlated with the system xc- activity.
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                Author and article information

                Contributors
                zjj2521@sina.com
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                19 June 2017
                July 2017
                : 6
                : 7 ( doiID: 10.1002/cam4.2017.6.issue-7 )
                : 1686-1697
                Affiliations
                [ 1 ] Department of Oral and Maxillofacial Surgery Stomatological Hospital of Southern Medical University & Guangdong Provincial Stomatological Hospital Southern Medical University Guangzhou 510260 Guangdong China
                [ 2 ] Department of Stomatology Guizhou Provincial People's Hospital Guiyang 550002 Guizhou China
                [ 3 ] Department of Pathology Fudan University Shanghai Cancer Center Shanghai 200032 China
                [ 4 ] Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China
                Author notes
                [*] [* ] Correspondence

                Jianjiang Zhao, Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Southern Medical University & Guangdong Provincial Stomatological Hospital, Southern Medical University, No.366 South Jiangnan Avenue, Guangzhou, 510260, Guangdong, China. Tel/Fax: +86 020‐84439500; E‐mail: zjj2521@ 123456sina.com

                The authors contribute equally to this work

                Author information
                http://orcid.org/0000-0001-7417-196X
                Article
                CAM41110
                10.1002/cam4.1110
                5504333
                28627030
                dfcd702e-e90b-4666-ac9f-b5040469fe07
                © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 November 2016
                : 20 April 2017
                : 01 May 2017
                Page count
                Figures: 5, Tables: 1, Pages: 12, Words: 5537
                Funding
                Funded by: Youth Foundation of Guizhou Provincial People's Hospital
                Award ID: GZSYQN[2016]07
                Categories
                Original Research
                Cancer Biology
                Original Research
                Custom metadata
                2.0
                cam41110
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.3 mode:remove_FC converted:11.07.2017

                Oncology & Radiotherapy
                mir‐375,oscc,slc7a11
                Oncology & Radiotherapy
                mir‐375, oscc, slc7a11

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