The Fudan University Shanghai Cancer Center (FUSCC, Chinese: 复旦大学附属肿瘤医院), also called the Shanghai Cancer Hospital (Chinese: 上海市肿瘤医院), is a teaching hospital affiliated with the Shanghai Medical College of Fudan University. Founded in 1931, it is the first cancer specialty hospital in China. It is rated Grade 3, Class A.
Cancer metabolic reprogramming generates a hostile tumor microenvironment (TME) characterized by lactate-driven acidosis, fostering tumor progression. Epstein-Barr virus (EBV), an oncogenic herpesvirus linked to multiple malignancies, thrives under such stress, yet how it interacts with and contributes to an acidic TME remains poorly understood. Here, we identify miR-7-5p as a lactate-downregulated microRNA with diagnostic potential in plasma from patients with EBV-associated diffuse large B cell lymphoma and nasopharyngeal carcinoma. TRIM33, a previously uncharacterized lactate-inducible transcriptional regulator of glycolytic flux, is directly targeted by miR-7-5p. Integrative multi-omics analyses reveal that lactate promotes TRIM33 binding to specific motifs in the promoters of key glycolytic genes, including SLC16A1, which enhances their expression and reprograms metabolism. Importantly, the loss of TRIM33 accelerates tumor growth, enhances EBV reactivation, and confers resistance to lactate-transporter inhibitors. Our finding provides circulating miR-7-5p as a noninvasive biomarker and reveals TRIM33 as an integrator of lactate stress, metabolism, and viral oncogenesis, offering a novel dual-targeting therapeutic strategy.
