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      Anticancer effects of melatonin via regulating lncRNA JPX‐Wnt/β‐catenin signalling pathway in human osteosarcoma cells


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          Osteosarcoma (OS) is a type of malignant primary bone cancer, which is highly aggressive and occurs more commonly in children and adolescents. Thus, novel potential drugs and therapeutic methods are urgently needed. In the present study, we aimed to elucidate the effects and mechanism of melatonin on OS cells to provide a potential treatment strategy for OS. The cell survival rate, cell viability, proliferation, migration, invasion and metastasis were examined by trypan blue assay, MTT, colony formation, wound healing, transwell invasion and attachment/detachment assay, respectively. The expression of relevant lncRNAs in OS cells was determined by real‐time qPCR analysis. The functional roles of lncRNA JPX in OS cells were further examined by gain and loss of function assays. The protein expression was measured by western blot assay. Melatonin inhibited the cell viability, proliferation, migration, invasion and metastasis of OS cells (Saos‐2, MG63 and U2OS) in a dose‐dependent manner. Melatonin treatment significantly downregulated the expression of lncRNA JPX in Saos‐2, MG63 and U2OS cells. Overexpression of lncRNA JPX into OS cell lines elevated the cell viability and proliferation, which was accompanied by the increased metastasis. We also found that melatonin inhibited the OS progression by suppressing the expression of lncRNA JPX via regulating the Wnt/β‐catenin pathway. Our results suggested that melatonin inhibited the biological functions of OS cells by repressing the expression of lncRNA JPX through regulating the Wnt/β‐catenin signalling pathway, which indicated that melatonin might be applied as a potentially useful and effective natural agent in the treatment of OS.

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          Long Noncoding RNA and Cancer: A New Paradigm.

          In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.
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            RNA is not only a messenger operating between DNA and protein. Transcription of essentially the entire eukaryotic genome generates a myriad of non-protein-coding RNA species that show complex overlapping patterns of expression and regulation. Although long noncoding RNAs (lncRNAs) are among the least well-understood of these transcript species, they cannot all be dismissed as merely transcriptional "noise." Here, we review the evolution of lncRNAs and their roles in transcriptional regulation, epigenetic gene regulation, and disease.
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              Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified. Copyright © 2011 Elsevier Inc. All rights reserved.

                Author and article information

                jianyangdu@126.com , libo_career@163.com
                J Cell Mol Med
                J Cell Mol Med
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                21 September 2021
                October 2021
                : 25
                : 20 ( doiID: 10.1111/jcmm.v25.20 )
                : 9543-9556
                [ 1 ] Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China
                [ 2 ] Suzhou Research Institute Shandong University Suzhou Jiangsu China
                [ 3 ] Department of Orthopedics the First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang China
                [ 4 ] Department of Orthopedics Sun Yat‐Sen Memorial Hospital of Sun Yat‐Sen University Guangzhou China
                [ 5 ] Department of Neurosurgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong China
                Author notes
                [*] [* ] Correspondence

                Jianyang Du, Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.

                Email: jianyangdu@ 123456126.com

                Bo Li, Department of Orthopedics, Sun Yat‐Sen Memorial Hospital of Sun Yat‐Sen University, Guangzhou 510000, China.

                Email: libo_career@ 123456163.com

                Author information
                © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                : 03 August 2021
                : 27 February 2021
                : 11 August 2021
                Page count
                Figures: 7, Tables: 1, Pages: 14, Words: 9156
                Funded by: Shandong Province Medicine and Health Science and Technology Development Plan Project
                Award ID: 202002040581
                Funded by: the Graduate Innovation Fund of Harbin Medical University
                Award ID: YJSSJCX2019‐09HYD
                Funded by: Natural Science Foundation of Jiangsu Province
                Award ID: SBK2021042454
                Original Article
                Original Articles
                Custom metadata
                October 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.8 mode:remove_FC converted:12.10.2021

                Molecular medicine
                lncrnas,melatonin,osteosarcoma,therapeutic methods,wnt/β‐catenin pathway
                Molecular medicine
                lncrnas, melatonin, osteosarcoma, therapeutic methods, wnt/β‐catenin pathway


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