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      miR-541 serves as a prognostic biomarker of osteosarcoma and its regulatory effect on tumor cell proliferation, migration and invasion by targeting TGIF2

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          Abstract

          Background

          Several studies reported the dysregulation of miR-541 in the progression of some human malignancies. Osteosarcoma (OS) is one of the most common primary malignant bone tumors. This study aimed to assess the expression and clinical significance of miR-541 in OS patients and explore the biological function of miR-541 in tumor progression.

          Methods

          Expression of miR-541 was detected by quantitative real-time PCR, and its prognostic value was evaluated using Kaplan-Meier survival analysis. The biological function of miR-541 was examined by analyzing its effects on OS cell proliferation, migration and invasion. Additionally, the underlying potential target of miR-541 was predicated and analyzed.

          Results

          The expression of miR-541 was significantly decreased in OS tissues and cell lines. The deregulated expression of miR-541 in tumor tissues was associated with the overall survival of OS patients and was a potential independent prognostic indicator. In OS cells, the overexpression of miR-541 could inhibit cell proliferation, migration and invasion. The luciferase activity results indicated that TGIF2 was a potential target of miR-541.

          Conclusion

          The results of this study revealed that the decreased miR-541 expression in OS patients may serve as a prognostic biomarker, and that the overexpression of miR-541 in OS cells results in inhibited cell proliferation, migration and invasion, indicating the potential of miR-541 as a therapeutic target in OS treatment.

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          Most cited references26

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          Osteosarcoma Overview

          Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial. Noninvasive diagnostic methods include serum markers like alkaline phosphatase and a growing variety of imaging techniques including X-ray, computed tomography, magnetic resonance imaging, and positron emission as well as combinations thereof. Still, biopsy and microscopic examination are required to confirm the diagnosis and carry additional prognostic implications such as subtype classification and histological response to neoadjuvant chemotherapy. The current standard of care combines surgical and chemotherapeutic techniques, with a multitude of experimental biologics and small molecules currently in development and some in clinical trial phases. In this review, in addition to summarizing the current understanding of OS etiology, diagnostic methods, and the current standard of care, our group describes various experimental therapeutics and provides evidence to encourage a potential paradigm shift toward the introduction of immunomodulation, which may offer a more comprehensive approach to battling cancer pleomorphism.
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            Future directions in the treatment of osteosarcoma.

            Overall survival rates for osteosarcoma have remained essentially unchanged over the past 3 decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in the comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies.
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              Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage.

              Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.
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                Author and article information

                Contributors
                xiuling_yi1212@163.com
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central (London )
                1746-1596
                24 July 2020
                24 July 2020
                2020
                : 15
                : 96
                Affiliations
                GRID grid.416966.a, ISNI 0000 0004 1758 1470, Department of Spinal Surgery, , Weifang People’s Hospital, ; No. 151 Guangwen Street, Weifang, 261000 Shandong China
                Article
                1008
                10.1186/s13000-020-01008-9
                7379795
                32709240
                0316ae2f-a206-4713-9739-159897f945fd
                © 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/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 18 March 2020
                : 14 July 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Pathology
                osteosarcoma,microrna-541,prognosis,proliferation,migration,invasion,tgf-β-induced factor homeobox 2

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