Aberrant protein post-translational modification is a hallmark of malignant tumors. Lysine succinylation (Ksucc) plays a vital role in cell energy metabolism in various cancers. However, whether succinylation can be catalyzed by acetyltransferase p300 remains unclear. In this study, we unveiled that p300 is a “writer” for succinylation, and p300-mediated Ksucc promotes cell glycometabolism in lung adenocarcinoma (LUAD). Specifically, our succinylome data revealed that EP300 deficiency leads to the systemic reduction of Ksucc, and 79.55% of the p300-succinylated proteins were found in the cytoplasm, which were primarily enriched in the carbohydrate metabolism process. Interestingly, deleting EP300 led to a notable decrease in Ksucc levels on several glycolytic enzymes, especially Phosphoglycerate Kinase 1 (PGK1). Mutation of the succinylated site of PGK1 notably hindered cell glycolysis and lactic acid excretion. Metabolomics in vivo indicated that p300-caused metabolic reprogramming was mainly attributed to the altered carbohydrate metabolism. In addition, 89.35% of LUAD patients exhibited cytoplasmic localization of p300, with higher levels in tumor tissues than adjacent normal tissues. High levels of p300 correlated with advanced tumor stages and poor prognosis of LUAD patients. Briefly, we disclose the activity of p300 to catalyze succinylation, which contributes to cell glucose metabolic reprogramming and malignant progression of lung cancer.

Introduction: The role of SMU1 in DNA replication and RNA splicing is well-established, yet its specific function and dysregulated mechanisms in gastric cancer (GC) remain inadequately elucidated. This study seeks to investigate the potential oncogenic and progression-promoting effects of SMU1 in GC, with the ultimate goal of informing novel approaches for treatment and diagnosis. Methods: The study investigated the expression levels of SMU1 in GC and adjacent normal tissues by analyzing data from the TCGA (27 tissue pairs) and GEO (47 tissue pairs) databases. Immunohistochemistry was used to examine 277 tumor tissue and adjacent non-tumor tissue spots from GC tissue chips, along with relevant follow-up information. The study further assessed the proliferation, invasion, and migration capabilities of cells by manipulating SMU1 expression levels and conducting various assays, including CCK-8, EdU incorporation, colony formation, transwells, flow cytometry, and subcutaneous tumorigenesis assays. Results: Our study revealed a significant upregulation of SMU1 mRNA and protein levels in GC tissues compared to adjacent tissues. Univariate and multivariate Cox analysis demonstrated that elevated levels of SMU1 were independent prognostic factors for GC prognosis ( P = 0.036). Additionally, median survival analysis indicated a significant association between high SMU1 expression and poor prognosis in GC patients ( P = 0.0002). In experiments conducted both in vivo and in vitro, it was determined that elevated levels of SMU1 can enhance the proliferation, invasion, and migration of GC cells, whereas suppression of SMU1 can impede the progression of GC by modulating the G1/S checkpoint of the cell cycle. Conclusions: Our research introduces the novel idea that SMU1 could serve as a prognostic marker for GC progression, influencing cell proliferation through cell cycle activation. These results offer valuable insights into the understanding, diagnosis, and management of gastric carcinoma.

Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease. As stress-responsive membraneless organelles, stress granules (SGs) are involved in modulating inflammatory suppression and promoting tumorigenesis, but their role in the pathogenesis of CAC remains unclear. This study reveals that SGs exhibit a stage-specific function during CAC progression, being protective in acute colitis but transitioning to a tumor-promoting role in the dysplasia-carcinoma sequence. We first demonstrate that, during acute colitis, fluctuating oxidative stress drives dynamic SGs assembly. However, despite persistently elevated oxidative stress from chronic colitis to dysplasia, SGs levels paradoxically decline. This decline is attributed to the upregulation of TOM1, a novel negative regulator that binds the NTF2L domain of the core SGs scaffold protein G3BP1 to promote SGs disassembly, thereby counteracting the oxidative stress-driven assembly. The consequent disassembly facilitates the nuclear translocation of the oncogenic transcription factor FUBP1, which in turn promotes c-Myc expression and thereby contributes to tumorigenesis. Our findings establish the regulation of SGs dynamics, particularly via TOM1 and G3BP1, as a promising therapeutic strategy for CAC.

Diabetic retinopathy (DR) is among the most common microvascular complications of diabetes and is the leading cause of blindness among the working-age population. According to conventional perspectives, DR is a purely microvascular disease; however, accumulating evidence has demonstrated that it is fundamentally a complex condition characterized by coordinated multicellular injury to the retinal neurovascular unit. Under hyperglycemic conditions, retinal pericytes, endothelial cells, Müller cells, microglia, and retinal neurons display highly heterogeneous pathological mechanisms, which, through epigenetic reprogramming, metabolic dysregulation, oxidative stress, inflammation, and intercellular crosstalk, collectively drive the progression of DR from nonproliferative to proliferative stages. This review summarizes the cell-heterogeneous injury mechanisms and intercellular signaling networks involved and the clinical manifestations of DR progression from the perspective of cell and molecular medicine and, on the basis of relevant cellular damage targets, integrates current diagnostic and therapeutic strategies as well as emerging research directions, aiming to provide a theoretical foundation for precise targeting of multicellular pathological processes in DR.