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      Roles of miRNA dysregulation in the pathogenesis of multiple myeloma

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          Abstract

          Multiple myeloma (MM) is a malignant disease of plasma cells with complex pathology, causing significant morbidity due to its end-organ destruction. The outcomes of patients with myeloma have significantly improved in the past couple of decades with the introduction of novel agents, such as proteasome inhibitors, immunomodulators, and monoclonal antibodies. However, MM remains incurable and presents considerable individual heterogeneity. MicroRNAs (miRNAs) are short, endogenous noncoding RNAs of 19–22 nucleotides that regulate gene expression at the posttranscriptional level. Numerous studies have shown that miRNA deregulation is closely related to MM pathology, including tumor initiation, progression, metastasis, prognosis, and drug response, which make the complicated miRNA network an attractive and marvelous area of investigation for novel anti-MM therapeutic approaches. Herein, we mainly summarized the current knowledge on the roles of miRNAs, which are of great significance in regulating pathological factors involved in MM progressions, such as bone marrow microenvironment, methylation, immune regulation, genomic instability, and drug resistance. Meanwhile, their potential as novel prognostic biomarkers and therapeutic targets was also discussed.

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          Most cited references138

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          Microenvironmental regulation of tumor progression and metastasis.

          Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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            The widespread regulation of microRNA biogenesis, function and decay.

            MicroRNAs (miRNAs) are a large family of post-transcriptional regulators of gene expression that are approximately 21 nucleotides in length and control many developmental and cellular processes in eukaryotic organisms. Research during the past decade has identified major factors participating in miRNA biogenesis and has established basic principles of miRNA function. More recently, it has become apparent that miRNA regulators themselves are subject to sophisticated control. Many reports over the past few years have reported the regulation of miRNA metabolism and function by a range of mechanisms involving numerous protein-protein and protein-RNA interactions. Such regulation has an important role in the context-specific functions of miRNAs.
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              MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation.

              MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 5'TOP motif and that the 5'TOP regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.
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                Author and article information

                Contributors
                zzhangzhihua@163.com
                xeh001@sina.com
                Journal
                Cancer Gene Ther
                Cancer Gene Ther
                Cancer Gene Therapy
                Nature Publishing Group US (New York )
                0929-1903
                1476-5500
                5 January 2021
                5 January 2021
                2021
                : 28
                : 12
                : 1256-1268
                Affiliations
                [1 ]GRID grid.413368.b, Department of Central Laboratory, , The Affiliated Hospital of Chengde Medical College, ; Chengde, Hebei China
                [2 ]GRID grid.413368.b, Department of Hematology, , The Affiliated Hospital of Chengde Medical College, ; Chengde, Hebei China
                Author information
                http://orcid.org/0000-0003-2396-0314
                http://orcid.org/0000-0002-9806-7355
                Article
                291
                10.1038/s41417-020-00291-4
                8636266
                33402729
                da0fdd42-cbfb-4689-a0bc-eda662af2aaa
                © The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature 2021

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 September 2020
                : 3 December 2020
                : 11 December 2020
                Funding
                Funded by: Chengde Technology Research and Development Program (No. 201804A079).
                Categories
                Review Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021

                Oncology & Radiotherapy
                myeloma,gene regulation
                Oncology & Radiotherapy
                myeloma, gene regulation

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