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      Upregulated expression of miR-421 is associated with poor prognosis in non-small-cell lung cancer

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          Abstract

          Background

          Non-small-cell lung cancer (NSCLC) represents the most frequent subtype of lung cancer. MicroRNAs (miRNAs) have attracted a lot of attention with regard to their clinical significance and crucial biological functions in various human cancers. This study aimed to investigate the prognostic significance of microRNA-421 (miR-421) and its correlation with tumor progression in NSCLC.

          Materials and methods

          Expression levels of miR-421 in both serum and tissue samples were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The prognostic value of miR-421 was evaluated using Kaplan–Meier survival analysis and Cox regression assay. To explore the functional role of miR-421 during NSCLC progression, cell experiments were carried out.

          Results

          Expression of serum and tissue miR-421 was upregulated in the NSCLC patients compared with the normal controls (all P<0.001), and the expression showed a significant correlation between the serum samples and tissues ( R=0.475, P<0.001). The increased miR-421 expression was associated with positive lymph-node metastasis and advanced TNM stage (all P<0.05). Moreover, patients with high miR-421 expression had poor overall survival compared with those with low expression (log-rank P=0.007). The overexpression of miR-421 proved to be an independent prognostic factor for NSCLC (HR=1.991, 95% CI=1.046–3.791, P=0.036). According to the cell experiments, the proliferation, migration and invasion of NSCLC cells were suppressed by knockdown of miR-421.

          Conclusion

          Overexpression of miR-421 serves as a prognostic biomarker and may be involved in the promotion of tumor progression in NSCLC.

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          Most cited references28

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          MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer.

          MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 60% of all human genes. They play important roles in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes. In this study, the authors demonstrated that miRNA-205 (miR-205) induced the expression the interleukin (IL) tumor suppressor genes IL24 and IL32 by targeting specific sites in their promoters. The methods used in this study included transfection of small RNAs; quantitative real-time polymerase chain reaction; in situ hybridization; fluorescence-labeled in situ hybridization; cell cycle, apoptosis, cell viability, migratory, clonability, and invasion assays; immunoblotting; and luciferase reporter, nuclear run-on, and chromatin immunoprecipitation assays. The results revealed that miR-205 was silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability, and invasiveness of prostate cancer cells. Micro-RNA-205 induced the expression of tumor suppressor genes IL24 and IL32 at both the messenger RNA and protein levels. The induction of in vitro transcription and enrichment of markers for transcriptionally active promoters in the IL24 and IL32 genes was observed in response to miR-205. In this study, a new function for miR-205 was identified that specifically activated tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a newly identified function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (eg, IL24, IL32) or other dysregulated genes by miRNA may contribute to a novel therapeutic approach for the treatment of prostate cancer. Copyright © 2010 American Cancer Society.
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            Adjuvant chemotherapy for resected early-stage non-small cell lung cancer

            To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010.
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              The association between lung cancer incidence and ambient air pollution in China: A spatiotemporal analysis.

              China is experiencing more and more days of serious air pollution recently, and has the highest lung cancer burden in the world.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                Cancer Management and Research
                Cancer Management and Research
                Dove Medical Press
                1179-1322
                2018
                13 August 2018
                : 10
                : 2627-2633
                Affiliations
                [1 ]Department of Clinical Laboratory, Shouguang People’s Hospital, Shandong 262700, China, yunxiali_dor@ 123456163.com
                [2 ]Department of Neurosurgery, Shouguang People’s Hospital, Shandong 262700, China
                [3 ]Department of Joint Surgery, Shouguang People’s Hospital, Shandong 262700, China
                [4 ]Hemodialysis Room, Shouguang People’s Hospital, Shandong 262700, China
                [5 ]Coronary Care Unit, Shouguang People’s Hospital, Shandong 262700, China
                Author notes
                Correspondence: Yunxia Li, Clinical Laboratory, Shouguang People’s Hospital, No. 1233 Jiankang Road, Shouguang 262700, China, Email yunxiali_dor@ 123456163.com
                Article
                cmar-10-2627
                10.2147/CMAR.S167432
                6095112
                cccfbe56-0d7c-4106-8ba2-bdadaee21f7a
                © 2018 Li et al. 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.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                mir-421,prognosis,progression,non-small-cell lung cancer
                Oncology & Radiotherapy
                mir-421, prognosis, progression, non-small-cell lung cancer

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