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      MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

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          Abstract

          Aim

          To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism.

          Methods

          The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial–mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-β is the target gene of miR-296-5p. Finally, TGF-β expression plasmids were transfected into NPC cells to verify the role of TGF-β in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis.

          Results

          Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-β, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-β and was significantly associated with the lymph node metastasis of patients with NPC.

          Conclusions

          Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-β. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

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          Most cited references39

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            Cancer statistics, 2016.

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population.
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              Characteristics and Significance of the Pre-metastatic Niche

              Primary tumors create a favorable microenvironment, namely, pre-metastatic niche, in secondary organs and tissue sites for subsequent metastases. The pre-metastatic niche can be primed and established through a complex interplay among primary tumor-derived factors, tumor-mobilized bone marrow-derived cells, and local stromal components. We review here our current understanding of the key components and underlying mechanisms for pre-metastatic niche formation. We propose six characteristics that define the pre-metastatic niche, which enable tumor cell colonization and promote metastasis, including immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, and reprogramming. We highlight the significance of the pre-metastatic niche, and discuss potential implications and future research directions.
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                Author and article information

                Contributors
                tangxudong2599@126.com
                xyli75@126.com
                Journal
                Cell Mol Biol Lett
                Cell Mol Biol Lett
                Cellular & Molecular Biology Letters
                BioMed Central (London )
                1425-8153
                1689-1392
                3 November 2020
                3 November 2020
                2020
                : 25
                : 49
                Affiliations
                [1 ]GRID grid.410560.6, ISNI 0000 0004 1760 3078, Institute of Biochemistry and Molecular Biology of Guangdong Medical University, ; No. 2 Wenming Dong Road, Xiashan District, Zhanjiang, 524023 Guangdong China
                [2 ]Department of Clinical Laboratory of Zhanjiang Central Hospital, Zhanjiang, 524023 China
                [3 ]GRID grid.410560.6, ISNI 0000 0004 1760 3078, Center of Oncology of The Affiliated Hospital of Guangdong Medical University, ; Zhanjiang, 524023 China
                Article
                240
                10.1186/s11658-020-00240-x
                7640465
                33292168
                8e9efbf7-5a32-47bb-b1c9-938363b363d4
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 April 2020
                : 26 October 2020
                Funding
                Funded by: Guangdong sails Project High level Talent Project
                Award ID: 4YF17001G
                Award Recipient :
                Funded by: Special funds for Science and Technology Innovation Strategy of Guangdong Province
                Award ID: 2018A030310155
                Award Recipient :
                Funded by: “Group-type” Special Supporting Project for Educational Talents in Universities
                Award ID: 4SG19057G
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                mir-296-5p,metastasis,invasion,emt,nasopharyngeal carcinoma
                mir-296-5p, metastasis, invasion, emt, nasopharyngeal carcinoma

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