Background Histone deacetylases (HDACs) have been shown to be involved in tumorigenesis, but their precise role and molecular mechanisms in gastric cancer (GC) have not yet been fully elucidated. Methods Bioinformatics screening analysis, qRT-PCR, and immunohistochemistry (IHC) were used to identify the expression of HDAC4 in GC. In vitro and in vivo functional assays illustrated the biological function of HDAC4. RNA-seq, GSEA pathway analysis, and western blot revealed that HDAC4 activated p38 MAPK signalling. Immunofluorescence, western blot, and IHC verified the effect of HDAC4 on autophagy. ChIP and dual-luciferase reporter assays demonstrated that the transcriptional regulation mechanism of HDAC4 and ATG4B. Results HDAC4 is upregulated in GC and correlates with poor prognosis. In vitro and in vivo assays showed that HDAC4 contributes to the malignant phenotype of GC cells. HDAC4 inhibited the MEF2A-driven transcription of ATG4B and prevented MEKK3 from p62-dependent autophagic degradation, thus activating p38 MAPK signalling. Reciprocally, the downstream transcription factor USF1 enhanced HDAC4 expression by regulating HDAC4 promoter activity, forming a positive feedback loop and continuously stimulating HDAC4 expression and p38 MAPK signalling activation. Conclusion HDAC4 plays an oncogenic role in GC, and HDAC4-based targeted therapy would represent a novel strategy for GC treatment.

Background Fatty acid‐binding proteins (FABPs) have been found to be involved in tumorigenesis and development. However, the role of FABP4, a member of the FABPs, in GISTs (Gastrointestinal stromal tumors) remains unclear. This study aimed to investigate the expression of FABP4 and its prognostic value in GISTs. Methods FABP4 expression in 125 patients with GISTs was evaluated by immunohistochemical analysis of tissue microarrays. The relationship between FABP4 expression and clinicopathological features and prognosis of GISTs was analyzed. Results Multiple logistic regression analysis showed that expression of FABP4 correlated with tumor size and mitotic index. Furthermore, FABP4 level, tumor size, mitotic index, and high AFIP‐Miettinen risk were independent prognostic factors in GISTs. The Kaplan‐Meier survival curve showed that the 5‐year survival rate of patients with high‐FABP4 expression GISTs was lower. Conclusions These results suggested that high‐FABP4 expression might be a marker of malignant phenotype of GISTs and poor prognosis.