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      The effect of miR-539 regulating TRIAP1 on the apoptosis, proliferation, migration and invasion of osteosarcoma cells

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          Abstract

          Objective

          The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma (OS) and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma.

          Method

          miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apaf1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo.

          Results

          After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group ( P < 0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group ( P < 0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group ( P < 0.01).

          Conclusions

          MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.

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          Osteosarcoma treatment - where do we stand? A state of the art review.

          Ian Lewis, Anja Luetke, Steven P. Meyers … (2014)
          Long-term outcome for patients with high-grade osteosarcoma has improved with the addition of systemic chemotherapy, but subsequent progress has been less marked. Modern, multiagent, dose-intensive chemotherapy in conjunction with surgery achieves a 5-year event-free survival of 60-70% in extremity localized, non-metastatic disease. A major, as yet unsolved, problem is the poor prognosis for metastatic relapse or recurrence, and for patients with axial disease. This article reviews the current state of the art of systemic osteosarcoma therapy by focusing on the experiences of cooperative osteosarcoma groups. Also, we shed light on questions and challenges posed by the aggressiveness of the tumor, and we consider potential future directions that may be critical to progress in the prognosis of high-grade osteosarcoma. Copyright © 2014. Published by Elsevier Ltd.
          Article 0 comments Cited 256 times – based on 0 reviews     Review now
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            MicroRNAs and complex diseases: from experimental results to computational models

            Qi Zhao, Di Xie, Xing Guo Chen … (2017)
            Plenty of microRNAs (miRNAs) were discovered at a rapid pace in plants, green algae, viruses and animals. As one of the most important components in the cell, miRNAs play a growing important role in various essential and important biological processes. For the recent few decades, amounts of experimental methods and computational models have been designed and implemented to identify novel miRNA-disease associations. In this review, the functions of miRNAs, miRNA-target interactions, miRNA-disease associations and some important publicly available miRNA-related databases were discussed in detail. Specially, considering the important fact that an increasing number of miRNA-disease associations have been experimentally confirmed, we selected five important miRNA-related human diseases and five crucial disease-related miRNAs and provided corresponding introductions. Identifying disease-related miRNAs has become an important goal of biomedical research, which will accelerate the understanding of disease pathogenesis at the molecular level and molecular tools design for disease diagnosis, treatment and prevention. Computational models have become an important means for novel miRNA-disease association identification, which could select the most promising miRNA-disease pairs for experimental validation and significantly reduce the time and cost of the biological experiments. Here, we reviewed 20 state-of-the-art computational models of predicting miRNA-disease associations from different perspectives. Finally, we summarized four important factors for the difficulties of predicting potential disease-related miRNAs, the framework of constructing powerful computational models to predict potential miRNA-disease associations including five feasible and important research schemas, and future directions for further development of computational models.
            Article 0 comments Cited 188 times – based on 0 reviews     Review now
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              MicroRNAs in B-cell lymphomas: how a complex biology gets more complex.

              K Musilova, M Mraz (2015)
              MicroRNAs (miRNAs) represent important regulators of gene expression besides transcriptional control. miRNA regulation can be involved in the cell developmental fate decisions, but can also have more subtle roles in buffering stochastic fluctuations in gene expression. They participate in pathways fundamental to B-cell development like B-cell receptor (BCR) signalling, B-cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins. miRNAs influence B-cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and memory B cells. In this review, we discuss miRNAs with essential functions in malignant B-cell development (such as miR-150, miR-155, miR-21, miR-34a, miR-17-92 and miR-15-16). We also put these miRNAs in the context of normal B-cell differentiation, as this is intimately connected to neoplastic B-cell development. We review miRNAs' role in the most common B-cell malignancies, including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). We focus on miR-contribution to the regulation of important signalling pathways (such as NF-κB, PI3K/AKT and TGF-β), BCR signalling and its modulators (such as PTEN, SHIP-1, ZAP-70, GAB1 and BTK), anti- and pro-apoptotic proteins (such as BCL2, MCL1, TCL1, BIM, p53 and SIRT1) and transcription factors (such as MYC, MYB, PU.1, FOXP1 and BCL6). We also discuss the association of miRNAs' expression levels with the patients' survival and response to therapy, summarizing their potential use as predictive and prognostic markers. Importantly, the targeting of miRNAs (like use of anti-miR-155 or miR-34a mimic) could provide a novel therapeutic approach as evidenced by tumour regression in xenograft mouse models and initial promising data from clinical trials.
              Article 0 comments Cited 101 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Lin Cai:
                ORCID: http://orcid.org/0000-0003-3126-6429
                orthopedics@whu.edu.cn
                Journal
                Journal ID (nlm-ta): Cancer Cell Int
                Journal ID (iso-abbrev): Cancer Cell Int
                Title: Cancer Cell International
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2867
                Publication date (Electronic): 20 April 2021
                Publication date PMC-release: 20 April 2021
                Publication date Collection: 2021
                Volume: 21
                Electronic Location Identifier: 227
                Affiliations
                [1 ]GRID grid.413247.7, Department of Spine Surgery and Musculoskeletal Tumor, , Zhongnan Hospital of Wuhan University, ; Wuhan, People’s Republic of China
                [2 ]GRID grid.452823.a, Department of Joint Surgery, , Jiangxi Pingxiang People’s Hospital, ; Pingxiang, People’s Republic of China
                Author information
                http://orcid.org/0000-0003-3126-6429
                Article
                Publisher ID: 1909
                DOI: 10.1186/s12935-021-01909-9
                PMC ID: 8056639
                PubMed ID: 33879126
                SO-VID: c04f3135-5dae-437d-944b-c0f8ffb2abeb
                Copyright © © The Author(s) 2021
                License:

                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
                Date received : 20 December 2020
                Date accepted : 7 April 2021
                Categories
                Subject: Primary Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mirna-539,triap1,osteosarcoma,cell proliferation
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mirna-539, triap1, osteosarcoma, cell proliferation

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