The imbalance between acetylation and deacetylation of histone proteins, important for epigenetic modifications, is closely associated with various diseases, including cancer. However, knowledge regarding the modification of histones across the different types of digestive cancers is still lacking. The purpose of this research was to analyze the role of histone acetylation and deacetylation in pan-digestive cancers. We systematically characterized the molecular alterations and clinical relevance of 13 histone acetyltransferase (HAT) and 18 histone deacetylase (HDAC) genes in five types of digestive cancers, including esophageal carcinoma, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Recurrent mutations and copy number variation (CNV) were extensively found in acetylation-associated genes across pan-digestive cancers. HDAC9 and KAT6A showed widespread copy number amplification across five pan-digestive cancers, while ESCO2, EP300, and HDAC10 had prevalent copy number deletions. Accordingly, we found that HAT and HDAC genes correlated with multiple cancer hallmark-related pathways, especially the histone modification-related pathway, PRC2 complex pathway. Furthermore, the expression pattern of HAT and HDAC genes stratified patients with clinical benefit in hepatocellular carcinoma and pancreatic cancer. These results indicated that acetylation acts as a key molecular regulation of pan-digestive tumor progression.

Purpose: The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD.Methods: The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B.Results: In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial–mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions.Conclusions: Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment.

Distant metastasis is a primary factor contributing to the significantly shorter survival time of patients with advanced lung adenocarcinoma. The transcription factor Kruppel-like factor 5 (KLF5) facilitates the progression of lung adenocarcinoma. However, the specific mechanism by which KLF5 is involved in the tumor metastasis of lung adenocarcinoma metastasis remains largely unclear. Using bioinformatic analysis, Rhophilin Rho GTPase Binding Protein 2 (RHPN2) was identified as a potential downstream target gene for KLF5; it plays a crucial role in the regulation of the epithelial-mesenchymal transformation pathway in lung adenocarcinoma. Western blotting and immunohistochemistry were performed to examine RHPN2 expression in lung adenocarcinoma. In vivo and in vitro experiments were conducted to explore the regulatory role of RHPN2 on the cell growth and metastasis of lung adenocarcinoma. Chromatin immunoprecipitation sequencing was used to analyze the direct binding activity between KLF5 and RHPN2 promoter regions. Luciferase activity assay was performed to verify the transcriptional activation effect of KLF5 on RHPH2. RHPN2 was highly expressed in lung adenocarcinoma; patients with lung adenocarcinoma who showed high RHPN2 expression had a poor prognosis. In vivo and in vitro experiments showed that RHPN2 promoted cell growth and metastasis and activated the epithelial-mesenchymal transformation pathway in lung adenocarcinoma. KLF5 directly bound to the promoter region of RHPN2 and upregulated its expression in lung adenocarcinoma through transcriptional activation. In addition, rescue experiments confirmed that KLF5 facilitated the progression of lung adenocarcinoma in an RHPN2-dependent manner. Our study offers insights into the potential mechanisms of metastasis in lung adenocarcinoma and highlights RHPN2 as a potential therapeutic target.