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      GINS2 Promotes Osteosarcoma Tumorigenesis via STAT3/MYC Axis

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          Abstract

          GINS2 is overexpressed in several cancers, but little is known about its role in osteosarcoma (OS). A series of in vivo and in vitro experiments were conducted to explore the role of GINS2 in OS. In this study, we demonstrated that GINS2 was found to be highly expressed in OS tissues and cell lines, which was associated with poor outcomes in OS patients. GINS2 knockdown hindered the growth and induced apoptosis in OS cell lines in vitro. Furthermore, GINS2 knockdown effectively inhibited the growth of a xenograft tumor in vivo. By using an Affymetrix gene chip and intelligent pathway analysis, it was demonstrated that the GINS2 knockdown could reduce the expression of several targeted genes and reduce the activity of the MYC signaling pathway. Mechanically, LC-MS, CoIP, and rescue experiments revealed that GINS2 promoted tumor progression through the STAT3/MYC axis in the OS. Moreover, GINS2 was associated with tumor immunity and may be a potential immunotherapeutic target for OS.

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          Most cited references31

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          MYC on the path to cancer.

          The MYC oncogene contributes to the genesis of many human cancers. Recent insights into its expression and function have led to therapeutic opportunities. MYC's activation by bromodomain proteins could be inhibited by drug-like molecules, resulting in tumor inhibition in vivo. Tumor growth can also be curbed by pharmacologically uncoupling bioenergetic pathways involving glucose or glutamine metabolism from Myc-induced cellular biomass accumulation. Other approaches to halt Myc on the path to cancer involve targeting Myc-Max dimerization or Myc-induced microRNA expression. Here the richness of our understanding of MYC is reviewed, highlighting new biological insights and opportunities for cancer therapies. Copyright © 2012 Elsevier Inc. All rights reserved.
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            STATs in cancer inflammation and immunity: a leading role for STAT3.

            Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.
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              Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.

              Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                jo
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2023
                23 February 2023
                : 2023
                : 8454142
                Affiliations
                1Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, China
                2Department of Orthopedics, The Yiwu Central Hospital, Jinhua, Zhejiang, China
                Author notes

                Academic Editor: Jiang Pi

                Author information
                https://orcid.org/0000-0001-8463-4526
                https://orcid.org/0000-0002-1785-1966
                https://orcid.org/0000-0003-3035-171X
                https://orcid.org/0000-0002-0243-9709
                https://orcid.org/0000-0001-9747-7005
                https://orcid.org/0000-0002-5819-0519
                https://orcid.org/0000-0001-5834-1834
                Article
                10.1155/2023/8454142
                9981285
                36873736
                19a55df8-1670-49ee-8b31-93b8ac4e9f01
                Copyright © 2023 Bingkai Ren et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 June 2022
                : 6 September 2022
                : 25 November 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81760488
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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