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      Circular RNA 100146 functions as an oncogene through direct binding to miR-361-3p and miR-615-5p in non-small cell lung cancer

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          Abstract

          Circular RNAs are widely expressed in eukaryotic cells and associated with cancer. However, limited studies to date have focused on the potential role of circRNAs in progression of lung cancer. Data from the current investigation showed that circRNA 100146 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and the chemically induced malignant transformed bronchial cell line, 16HBE-T, as well as 40 paired tissue samples of NSCLC. Suppression of circRNA 100146 inhibited the proliferation and invasion of cells and promoted apoptosis. Furthermore, circRNA 100146 could interact with splicing factors and bind miR-361-3p and miR-615-5p to regulate multiple downstream mRNAs. Our collective findings support a role of circRNA 100146 in the development of NSCLC and further demonstrate endogenous competition among circRNA 100146, SF3B3 and miRNAs, providing novel insights into the mechanisms underlying non-small cell lung cancer.

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          The online version of this article (10.1186/s12943-019-0943-0) contains supplementary material, which is available to authorized users.

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          Altered miRNA expression profiles and miR-1a associated with urethane-induced pulmonary carcinogenesis.

          MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene expression. Previous research has suggested that aberrant miRNA expression often plays a critical role in many types of cancer, including lung cancer. However, the exact miRNAs that are involved in pulmonary carcinogenesis remain unclear. We investigated the miRNA-based molecular changes that occur in urethane-induced carcinogenicity and identified specific miRNA deregulation in pulmonary carcinogenesis induced by urethane. In this study, we used a lung cancer model in which Balb/c mice were exposed to urethane via ip injection once a week for four consecutive weeks. The mice were then killed in weeks 6, 12, or 24. Two small RNA libraries were constructed with the total RNA from the lung tumor and normal adjacent lung tissues of the urethane-injected mice collected in week 24. Using Solexa sequencing, we identified a plethora of differentially expressed miRNAs and predicted nine novel miRNAs. Further analysis demonstrated the sustainable downregulation of miR-1a in the lung tissues in lung carcinogenesis induced by urethane. The levels of miR-1a were also reduced in the serum. Our findings indicate that urethane exposure alters the expression of a cluster of miRNAs. The simultaneous downregulation of miR-1a in lung tissues and serum in urethane-induced pulmonary carcinogenesis suggests that miR-1a is associated with tumorigenesis.
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            Author and article information

            Contributors
            1198148914@qq.com
            584720116@qq.com
            nanzhang926@126.com
            jyyang69@126.com
            995264825@qq.com
            ling_yh@163.com
            daijbin@163.com
            shaozhucheung@126.com
            yqy1208@126.com
            yiyeni22@163.com
            +86 2037103535 , jiangyiguo@vip.163.com , jiangyiguo@gzhmu.edu.cn
            Journal
            Mol Cancer
            Mol. Cancer
            Molecular Cancer
            BioMed Central (London )
            1476-4598
            21 January 2019
            21 January 2019
            2019
            : 18
            : 13
            Affiliations
            [1 ]GRID grid.470124.4, State Key Laboratory of Respiratory Disease, , The First Affiliated Hospital of Guangzhou Medical University, ; Guangzhou, 510120 People’s Republic of China
            [2 ]ISNI 0000 0000 8653 1072, GRID grid.410737.6, Institute for Chemical Carcinogenesis, Guangzhou Medical University, ; Guangzhou, People’s Republic of China
            Article
            943
            10.1186/s12943-019-0943-0
            6340182
            30665425
            1b594695-c2ae-40ca-a199-292a3bd59e3b
            © The Author(s). 2019

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

            History
            : 22 August 2018
            : 9 January 2019
            Funding
            Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
            Award ID: 81872652, 91643204, 81573180
            Award Recipient :
            Categories
            Letter to the Editor
            Custom metadata
            © The Author(s) 2019

            Oncology & Radiotherapy
            circrna,nsclc,splicing factor,microrna
            Oncology & Radiotherapy
            circrna, nsclc, splicing factor, microrna

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