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      Role of miR-520b in non-small cell lung cancer

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          Abstract

          The aim of the present study was to investigate the expression of microRNA (miR)-520b in non-small cell lung cancer (NSCLC) and its biological functions. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of miR-520b in 52 cases of NSCLC tissues, and its associations with tumor clinical staging and lymph node metastasis were analyzed. miR-520b mimics was transfected into A549 and Calu-3 cells. Cell proliferation, cell cycle, and cell invasion and migration abilities were assessed via cell counting kit-8 assay, flow cytometry and Transwell chamber assay, respectively. Western blot analysis was performed to detected protein expression levels, and dual luciferase reporter assay was used to detect the gene interaction. miR-520b expression was significantly downregulated in NSCLC. The expression of miR-520b in tumor tissues at N1 stage was lower than that at the N0 stage. miR-520b expression was negatively associated with clinical TNM staging. Furthermore, miR-520b mimic transfection inhibited the proliferation and invasion and metastasis abilities of A549 and Calu-3 cells. The expression of Rab22A was downregulated in the miR-520b mimics-transfected cells, whereas E-cadherin expression was increased, and vimentin expression was downregulated. Dual luciferase reporter assay demonstrated that miR-520b directly targeted the expression of Rab22A. Furthermore, Rab22A reversal downregulated the inhibitory effect of miR-520b. miR-520b expression was downregulated in NSCLC, which was negatively correlated with lymph node metastasis and TNM staging. miR-520b targeted on Rab22A to work as a tumor suppressor, inhibiting tumor proliferation and metastasis.

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          Most cited references35

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          Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis.

          Extracellular vesicles such as exosomes and microvesicles (MVs) are shed by cancer cells, are detected in the plasma of cancer patients, and promote cancer progression, but the molecular mechanisms regulating their production are not well understood. Intratumoral hypoxia is common in advanced breast cancers and is associated with an increased risk of metastasis and patient mortality that is mediated in part by the activation of hypoxia-inducible factors (HIFs). In this paper, we report that exposure of human breast cancer cells to hypoxia augments MV shedding that is mediated by the HIF-dependent expression of the small GTPase RAB22A, which colocalizes with budding MVs at the cell surface. Incubation of naïve breast cancer cells with MVs shed by hypoxic breast cancer cells promotes focal adhesion formation, invasion, and metastasis. In breast cancer patients, RAB22A mRNA overexpression in the primary tumor is associated with decreased overall and metastasis-free survival and, in an orthotopic mouse model, RAB22A knockdown impairs breast cancer metastasis.
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            Oncogenic miR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF-κB signaling pathway

            Background The primary issue arising from prostate cancer (PCa) is its high prevalence to metastasize to bone, which severely affects the quality of life and survival time of PCa patients. miR-210-3p is a well-documented oncogenic miRNA implicated in various aspects of cancer development, progression and metastasis. However, the clinical significance and biological roles of miR-210-3p in PCa bone metastasis remain obscure. Methods miR-210-3p expression was evaluated by real-time PCR in 68 bone metastatic and 81 non-bone metastatic PCa tissues. The biological roles of miR-210-3p in the bone metastasis of PCa were investigated both in vitro by EMT and Transwell assays, and in vivo using a mouse model of left cardiac ventricle inoculation. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to discern and examine the relationship between miR-210-3p and its potential targets. RT-PCR was performed to identify the underlying mechanism of miR-210-3p overexpression in bone metastasis of PCa. Clinical correlation of miR-210-3p with its targets was examined in human PCa and metastatic bone tissues. Results miR-210-3p expression is elevated in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Overexpression of miR-210-3p positively correlates with serum PSA levels, Gleason grade and bone metastasis status in PCa patients. Upregulating miR-210-3p enhances, while silencing miR-210-3p represses the EMT, invasion and migration of PCa cells in vitro. Importantly, silencing miR-210-3p significantly inhibits bone metastasis of PC-3 cells in vivo. Our results further demonstrate that miR-210-3p maintains the sustained activation of NF-κB signaling via targeting negative regulators of NF-κB signaling (TNF-α Induced Protein 3 Interacting Protein 1) TNIP1 and (Suppressor Of Cytokine Signaling 1) SOCS1, resulting in EMT, invasion, migration and bone metastasis of PCa cells. Moreover, our results further indicate that recurrent gains (amplification) contribute to miR-210-3p overexpression in a small number of PCa patients. The clinical correlation of miR-210-3p with SOCS1, TNIP1 and NF-κB signaling activity is verified in PCa tissues. Conclusion Our findings unravel a novel mechanism for constitutive activation of NF-κB signaling pathway in the bone metastasis of PCa, supporting a functional and clinical significance of epigenetic events in bone metastasis of PCa. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0688-6) contains supplementary material, which is available to authorized users.
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              MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer.

              Lung cancer is the most common cause of death in cancer worldwide, and cisplatin plays an important role in its treatment. However, the response to chemotherapy is poorly attributable to drug resistance. Our present study aimed to investigate the relation of the exosomal miR-146a-5p level with the chemosensitivity of NSCLC to cisplatin and the molecular mechanism that miR-146a-5p mediated to effect on chemotherapy response.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                November 2018
                12 September 2018
                12 September 2018
                : 16
                : 5
                : 3987-3995
                Affiliations
                [1 ]Respiratory Department, Shandong Chest Hospital, Jinan No. 5 People's Hospital, Jinan, Shandong 250000, P.R. China
                [2 ]Department of General Surgery, Jinan No. 5 People's Hospital, Jinan, Shandong 250000, P.R. China
                Author notes
                Correspondence to: Miss Linlin Zhang, Respiratory Department, Shandong Chest Hospital, 46 Lishan Road, Jinan, Shandong 250000, P.R. China, E-mail: zllbbl@ 123456163.com
                Article
                ETM-0-0-6732
                10.3892/etm.2018.6732
                6200959
                d1f89f94-03a0-4351-aca0-4d80b7df9143
                Copyright: © Zhang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 November 2017
                : 11 May 2018
                Categories
                Articles

                Medicine
                non-small cell lung cancer,microrna-520b,rab22a,tumor suppressor gene
                Medicine
                non-small cell lung cancer, microrna-520b, rab22a, tumor suppressor gene

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