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Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Highlights: Tight junctions are involved in malignant transformation of intestinal epithelial cells. Gap junctions are involved in malignant transformation of fibroblasts. LMOD1 is identified to resembles tight junctions in the epithelium and is similar to gap junctions in the stroma. LMOD1 regulates FGF1 expression in the stroma to promote tumorigenesis and is regulated by AKAP12 in the epithelium to inhibit tumorigenesis. LMOD1 is associated with low immunotherapy response rates in colorectal cancer patients. [ABSTRACT FROM AUTHOR]

The prognosis of patients with advanced arteriosclerosis is bleak due to the lack of understanding of arteriosclerosis. Epigenetics-based DNA methylation plays an important role in the pathogenesis of arteriosclerosis. Hence, we aimed to identify the epigenetics-related aberrantly methylated differentially expressed genes (AMDEGs) in arteriosclerosis. A gene expression dataset and DNA methylation dataset were downloaded from the Gene Expression Omnibus database, and AMDEGs were identified on the basis of the relationship between methylation and expression. Subsequently, the expression levels of candidate hub genes were detected in human peripheral blood mononuclear cells (PBMCs) from atherosclerotic patients and control subjects by RT-qPCR and Western blot. Lastly, the methylation level of the target gene was detected using the MassARRAY method. In the present study, the hypermethylated and downregulated genes were mainly involved in vascular smooth muscle contraction. The hypomethylated and upregulated genes were markedly associated with immune-inflammatory processes. Following validation, LMOD1 was identified as the target gene, which was hypermethylated and downregulated in arteriosclerosis. The methylation levels of CpG sites in LMOD1 promoter were detected to be elevated in the PBMCs of atherosclerotic patients. In conclusion, AMDEGs identified in the present study may assist in understanding the pathogenesis of arteriosclerosis. LMOD1 exhibits potential as a promising diagnostic and therapeutic biomarker for arteriosclerosis. [ABSTRACT FROM AUTHOR]

Background: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer.Methods: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data.Results: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor.Conclusion: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]