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There is hence an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up studies of 445 meningioma patients, we uncovered that CBX7 expression progressively decreases with malignancy grade and neoplasia stage in meningioma, and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC protein by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, consequently attenuates c-MYC-mediated transactivation of LDHA transcripts, and further inhibits glycolysis and subsequent cell proliferation. More importantly, the functional role of CBX7 was further confirmed in subcutaneous and orthotopic meningioma xenograft mouse models and meningioma patients. Altogether, our results shed light on the critical role of CBX7 in meningioma malignancy progression and identify the CBX7\/USP44\/c-MYC\/LDHA axis as a promising therapeutic target against meningioma progression.<\/jats:p>","DOI":"10.1093\/jmcb\/mjad057","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T08:10:20Z","timestamp":1696407020000},"source":"Crossref","is-referenced-by-count":7,"title":["CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44\/c-MYC\/LDHA axis"],"prefix":"10.1093","volume":"15","author":[{"given":"Haixia","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Fudan University , Shanghai 200032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyang","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 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