{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:21:16Z","timestamp":1791498076490,"version":"4.3.4"},"reference-count":71,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01 CA215452"],"award-info":[{"award-number":["R01 CA215452"]}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"crossref","award":["1R01EB026453"],"award-info":[{"award-number":["1R01EB026453"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100003287","name":"Rally Foundation","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100003287","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RP140022"],"award-info":[{"award-number":["RP140022"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,10]]},"abstract":"<jats:p>\n                    Osteosarcoma (OS) is the most common primary bone tumor of childhood. Approximately 20%\u201330% of OSs carry amplification of chromosome 8q24, which harbors the oncogene c-\n                    <jats:italic>MYC<\/jats:italic>\n                    and correlates with a poor prognosis. To understand the mechanisms that underlie the ability of MYC to alter both the tumor and its surrounding tumor microenvironment (TME), we generated and molecularly characterized an osteoblast-specific Cre-Lox-Stop-Lox-\n                    <jats:italic>\n                      c-Myc\n                      <jats:sup>T58A<\/jats:sup>\n                      p53\n                    <\/jats:italic>\n                    <jats:sup>fl\/+<\/jats:sup>\n                    <jats:italic\/>\n                    knockin genetically engineered mouse model (GEMM). Phenotypically, the\n                    <jats:italic>Myc<\/jats:italic>\n                    -knockin GEMM had rapid tumor development with a high incidence of metastasis. MYC-dependent gene signatures in our murine model demonstrated significant homology to the human hyperactivated MYC OS. We established that hyperactivation of MYC led to an immune-depleted TME in OS demonstrated by the reduced number of leukocytes, particularly macrophages. MYC hyperactivation led to the downregulation of macrophage colony-stimulating factor 1, through increased microRNA 17\/20a expression, causing a reduction of macrophage population in the TME of OS. Furthermore, we developed cell lines from the GEMM tumors, including a degradation tag\u2013MYC model system, which validated our MYC-dependent findings both in vitro and in vivo. Our studies utilized innovative and clinically relevant models to identify a potentially novel molecular mechanism through which MYC regulates the profile and function of the OS immune landscape.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.164947","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T15:36:41Z","timestamp":1686065801000},"source":"Crossref","is-referenced-by-count":34,"title":["MYC regulates CSF1 expression via microRNA 17\/20a to modulate tumor-associated macrophages in osteosarcoma"],"prefix":"10.1172","volume":"8","author":[{"given":"Bikesh K.","family":"Nirala","sequence":"first","affiliation":[{"name":"Texas Children\u2019s Cancer and Hematology Centers and The Faris D. Virani Ewing Sarcoma Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajhal D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Cancer and Hematology Centers and The Faris D. 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