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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      MiR-21-5p promotes the progression of non-small-cell lung cancer by regulating the expression of SMAD7

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      1 , 2
      OncoTargets and therapy
      Dove Medical Press
      MiR-21-5p, SMAD7, non-small-cell lung cancer, progression, MMP-9, E-cadherin

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          Abstract

          Objective

          The objective of this study was to detect the expression of MiR-21-5p in non-small-cell lung cancer (NSCLC) tissues, and to investigate the effect of its expression on the progression of NSCLC.

          Methods

          Real-time fluorescent quantitative PCR was used to detect the relative expression of MiR-21-5p in 118 NSCLC tumor tissues to their adjacent normal tissues. The expressions of SMAD7, MMP-9, E-cadherin, and vimentin proteins were detected by Western blotting or immunohistochemistry. Cell colony formation, scratch, and Transwell assays were used to detect the proliferation, migration, and invasion ability of A549 cells, respectively.

          Results

          MiR-21-5p was highly expressed in the tumor tissues of NSCLC patients, and its expression was significantly correlated with the clinical classification of NSCLC patients (χ 2=7.154, P=0.007), tumor size (χ 2=4.372, P=0.037), differentiation (χ 2=13.713, P=0.001), lymph node metastasis (χ 2=5.101, P=0.024), distant metastasis (χ 2=12.599, P=0.000), and TNM stage (χ 2=6.344, P=0.012), whereas it was positively correlated with the expression of SMAD7 protein ( r=0.669, P<0.05). The results of the luciferase gene reporter system showed that MiR-21-5p targeted and promoted the expression of SMAD7 gene, which enhanced NSCLC cell proliferation. Furthermore, MiR-21-5p promoted the expressions of MMP-9 and vimentin proteins as well as inhibited the expression of E-cadherin protein, which is associated with an elevated SMAD7 protein expression and enhanced the invasion/migration ability of NSCLC cells.

          Conclusion

          MiR-21-5p was highly expressed in NSCLC tumor tissues, and its high expression could promote NSCLC progression by targeting the expression of SMAD7.

          Most cited references20

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          MicroRNA as Biomarkers and Diagnostics.

          MicroRNAs (miRNAs) are a group of small non-coding RNAs that are involved in regulating a range of developmental and physiological processes; their dysregulation has been associated with development of diseases including cancer. Circulating miRNAs and exosomal miRNAs have also been proposed as being useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, miRNAs are discussed as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize some of the clinical evidence for the use of miRNAs as biomarkers in diagnostics and provide some general perspectives on their use in clinical situations. The analytical challenges in using miRNAs in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics.
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            Curcumin promotes apoptosis by activating the p53-miR-192-5p/215-XIAP pathway in non-small cell lung cancer.

            Curcumin has attracted increasing interest as an anti-cancer drug for decades. The mechanisms of action involve multiple cancer-related signaling pathways. Recent studies highlighted curcumin has epigenetic regulatory effects on miRNA in cancers. In the present study, we demonstrated the proapoptotic effects of curcumin in vitro and in vivo. miRNA microarray and qPCR indicated that miR-192-5p and miR-215 were the most responsive miRNAs upon curcumin treatment in H460 and A427 cells. Functional studies showed miR-192-5p/215 were putative tumor suppressors in non-small cell lung cancer. Curcumin also promoted miR-192-5p/215 expressions in A549 cells (p53 wild type) but not in H1299 cells (p53-null). Conditional knockdown of p53 by tetracycline inducible expression system significantly abrogated curcumin-induced miR-192-5p/215 upregulation in the p53 wild-type H460, A427 and A549 cells. Conversely, ectopic expression of exogenous wild-type but not R273H mutant p53 in the p53-null H1299 cells enabled miR-192-5p/215 response to curcumin treatment. The proapoptotic effects of curcumin also depended on miR-192-5p/215 induction, and antagonizing miR-192-5p/215 expression attenuated curcumin-induced apoptosis in H460, A427 and A549 cells, but not in H1299 cells. Finally, X-linked inhibitor of apoptosis (XIAP) is proved to be a novel transcriptional target of miR-192-5p/215. Taken together, this study highlights that the proapoptotic effects of curcumin depend on miR-192-5p/215 induction and the p53-miR-192-5p/215-XIAP pathway is an important therapeutic target for non-small cell lung cancer.
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              Epidemiology of lung cancer in China

              Background Lung cancer is the most common cancer and the leading cause of cancer death in China. Along with socioeconomic development, environmental problems have intensified and the burden of lung cancer continues to increase. Methods In this study, national cancer registry data was used for evaluating incidence, mortality, time trend, and prediction. Results In China in 2010, 605 900 patients were diagnosed and 486 600 patients died of lung cancer. Throughout the last three decades, the mortality of lung cancer has dramatically increased, as shown in national death surveys. From 2000 to 2010, age specific incidence of lung cancer increased in most age groups. It is estimated that in 2015, the total number of new cases of lung cancer will reach 733 300. Conclusions Lung cancer is a serious disease affecting public health and an effective control strategy is needed in China.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                28 November 2018
                : 11
                : 8445-8454
                Affiliations
                [1 ]Department of Oncology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei Province, People’s Republic of China
                [2 ]Department of Neurology, Chinese People’s Liberation Army, Wuhan General Hospital, Wuchang District, Wuhan, Hubei Province, People’s Republic of China, wuxiaofwhgh@ 123456163.com
                Author notes
                Correspondence: Xiaofei Wu, Department of Neurology, Chinese People’s Liberation Army, Wuhan General Hospital, 627 Wuluolu Street, Wuchang District, Wuhan, Hubei Province, People’s Republic of China, Tel +86 27 8804 1911, Email wuxiaofwhgh@ 123456163.com
                Article
                ott-11-8445
                10.2147/OTT.S172393
                6276624
                30568467
                92385a38-45d9-43db-9108-c6214503b6a1
                © 2018 Li and Wu. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Rapid Communication

                Oncology & Radiotherapy
                mir-21-5p,smad7,non-small-cell lung cancer,progression,mmp-9,e-cadherin
                Oncology & Radiotherapy
                mir-21-5p, smad7, non-small-cell lung cancer, progression, mmp-9, e-cadherin

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