Lactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation's role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens. Using TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens. We identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels. Lactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.

Gastric cancer is a type of malignant tumor that seriously threatens human life and health. Invasion and metastasis present difficulties in the treatment of gastric cancer, and the remodeling of the tumor cytoskeleton plays an important role in mediating the ability of tumor cells to achieve invasion and metastasis. Previous experimental results suggest that Celastrus orbiculatus extract can regulate cytoskeletal remodeling in gastric cancer, but the active component has not been determined. Betulonic acid, as an effective component of COE, inhibits the invasion and metastasis of gastric cancer cells by regulating cytoskeletal remodeling in vitro; its specific mechanisms have been studied here. After betulonic acid was dissolved, it was diluted to various working concentrations in RPMI-1640 medium and added to AGS, HGC-27 and GES-1 cell lines. Cell viability was assessed by CCK-8 and colony formation assays. Cytoskeleton staining was used to detect changes in cytoskeleton morphology. Functional assays including wound healing assays and transwell assays were used to detect the invasion and migration of cells. The effect of betulonic acid on cell invasion and migration was clearly and precisely observed by high-content imaging technology. Western blotting was used to detect the regulation of matrix metalloproteinase-related proteins and epithelial–mesenchymal transformation-related proteins. We found that betulonic acid inhibited the migration and invasion of gastric cancer cells. Therefore, betulonic acid inhibits the invasion and metastasis of gastric cancer cells by mediating cytoskeletal remodeling and regulating epithelial mesenchymal transformation.

Lung cancer, a leading cause of mortality worldwide, necessitates effective therapeutic strategies. Caragana jubata, a traditional Chinese medicinal plant, harbors Texasin, a potential anti-tumor agent. This study aimed to evaluate the anti-cancer effects of Texasin on lung cancer cells, while assessing its impact on normal lung cells. The study utilized cell lines H1299 and A549, alongside normal lung embryonic cells, to investigate Texasin's effects through Cell Counting Kit-8, Transwell, and wound healing assays. Transcriptome sequencing and analysis were performed to identify potential mechanisms. β-galactosidase activity and Retinoblastoma(RB) protein expression were assessed, and autophagy and apoptosis were explored through chloroquine co-treatment. Mice bearing H1299 cell-derived tumors were treated with Texasin. Tumor changes were assessed through in vivo imaging, and autophagy levels within the tumors were analyzed. Texasin inhibited lung cancer cell proliferation, migration, and invasion without harming normal cells. It promoted cell senescence, arrested the cell cycle in G1 phase, and upregulated β-galactosidase and RB protein expression. Texasin induced protective autophagy, which could be converted to apoptosis by chloroquine co-treatment. Texasin inhibits the proliferation of lung adenocarcinoma cells in vivo, as evidenced by immunohistochemistry showing an increase in autophagy levels within the tumors. Texasin emerges as a promising non-cytotoxic anti-lung adenocarcinoma cancer compound, significantly inhibiting malignant phenotypes, highlighting its potential for lung adenocarcinoma cancer therapy.

Chemoresistance remains a major obstacle limiting the therapeutic efficacy of gastric cancer treatments, and cytoskeleton remodeling together with the abnormal membrane localization of drug efflux proteins may contribute to resistance phenotypes. This study aimed to investigate the role of CD44v6 in gastric cancer chemoresistance and to clarify whether betulonic acid, an active monomeric component of Celastrus orbiculatus extract, can reverse drug resistance via CD44v6. Analysis of public databases and validation in clinical tissue samples revealed that CD44v6 was highly expressed in gastric cancer cells and associated with poor prognosis, whereas CD44v6 expression was positively regulated by polypyrimidine tract binding protein 1. CD44v6 expression was markedly upregulated in MKN-45/DDP and HGC-27/Oxaliplatin resistant cells. CD44v6 knockdown inhibited GC cell proliferation, colony formation, migration/invasion, and tumor growth and increased the sensitivity of resistant cells to DDP or oxaliplatin. Mechanistically, CD44v6 knockdown suppressed F-actin remodeling, pseudopodia formation, cell motility, and the phosphorylation of VASP, Ezrin/Radixin/Moesin and Cofilin. Multiplex immunofluorescence analysis of tissue microarrays, molecular docking, and coimmunoprecipitation confirmed that CD44v6 was coexpressed and interacted with Ezrin/Radixin/Moesin family proteins in gastric cancer tissues. Betulonic acid was identified as a candidate active monomer of Celastrus orbiculatus extract that could potentially bind to CD44v6. Treatment with betulonic acid inhibited the malignant biological behaviors of gastric cancer cells, increased chemosensitivity, reduced membrane-associated P-glycoprotein expression, and weakened the interaction between CD44v6 and ERM proteins. In MKN-45/DDP xenograft models, betulonic acid combined with DDP significantly inhibited tumor growth and partially alleviated DDP-associated toxicity. In conclusion, CD44v6 promotes gastric cancer chemoresistance by interacting with Ezrin/Radixin/Moesin proteins to regulate cytoskeleton remodeling and membrane-associated P-glycoprotein expression, whereas betulonic acid reverses DDP resistance by through the CD44v6-ERM axis. This study provides mechanistic evidence supporting betulonic acid as a potential chemosensitizer for gastric cancer treatment.