HDAC4 promotes the growth and metastasis of gastric cancer via autophagic degradation of MEKK3.

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.

Characterization of Volatile Compounds in Four Different Rhododendron Flowers by GC×GC-QTOFMS.

Volatile compounds in flowers of Rhododendron delavayi, R. agastum, R. annae, and R. irroratum were analyzed using comprehensive two-dimensional gas chromatography-mass spectrometry (GC×GC) coupled with high-resolution quadrupole time-of-flight mass spectrometry (QTOFMS). A significantly increased number of compounds was separated by GC×GC compared to conventional one-dimensional GC (1DGC), allowing more comprehensive understanding of the volatile composition of Rhododendron flowers. In total, 129 volatile compounds were detected and quantified. Among them, hexanal, limonene, benzeneacetaldehyde, 2-nonen-1-ol, phenylethyl alcohol, citronellal, isopulegol, 3,5-dimethoxytoluene, and pyridine are the main compounds with different content levels in all flower samples. 1,2,3-trimethoxy-5-methyl-benzene exhibits significantly higher content in R. irroratum compared to in the other three species, while isopulegol is only found in R. irroratum and R. agastum.