Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

Background Gastric cancer is a common and fatal disease with the highest incidence and mortality in men. Protocadherin beta 6 (PCDHB6) has not been reported much in tumors and the role of PCDHB6 in gastric cancer is not yet clear. Therefore, we aimed to investigate the expression of PCDHB6 in gastric cancer infiltration, invasion and metastasis and to assess the prognostic and functional significance of PCDHB6 in gastric cancer. Methods Based on TCGA, GEO database, bioinformatics analysis of PCDHB6 gene was performed from gene expression, survival analysis, gene mutation, immune infiltration, DNA methylation and enrichment analysis. In addition, Real-Time PCR was used to further confirm the role of PCDHB6 in gastric cancer. Results PCDHB6 gene was highly expressed in gastric cancer and positively correlated with poor patient prognosis. Real-Time PCR results also showed high expression of PCDHB6 in gastric cancer. PCDHB6 expression was positively correlated with tumor-associated fibroblasts, Basophils, CD4 + memory T-cells, CD8 + T- cells, Eosinophils, Macrophages, Regulatory T-cells and Type 2 T-helper cells were positively correlated with immune infiltration. KEGG and GO enrichment analysis showed that PCDHB6 gene was mainly involved in the regulation of Herpes simplex virus 1 infection, Hippo signaling pathway and cell adhesion pathway. Conclusions Our study comprehensive summary and analysis revealed for the first time that PCDHB6 is highly expressed in gastric cancer and is an oncogene. PCDHB6 can be used as a potential prognostic biomarker for gastric cancer and provides a powerful therapeutic target for the treatment of gastric cancer.

Background: Rotundine is an herbal medicine with anti-cancer effects. However, little is known about the anti-cancer effect of rotundine on colorectal cancer. Therefore, our study aimed to investigate the specific molecular mechanism of rotundine inhibition of colorectal cancer. Methods: MTT and cell scratch assay were performed to investigate the effects of rotundine on the viability, migration, and invasion ability of SW480 cells. Changes in cell apoptosis were analyzed by flow cytometry. DEGs were detected by high-throughput sequencing after the action of rotundine on SW480 cells, and the DEGs were subjected to function enrichment analysis. Bioinformatics analyses were performed to screen out prognosis-related DEGs of COAD. Followed by enrichment analysis of prognosis-related DEGs. Furthermore, prognostic models were constructed, including ROC analysis, risk curve analysis, PCA and t-SNE, Nomo analysis, and Kaplan–Meier prognostic analysis. Results: In this study, we showed that rotundine concentrations of 50 μM, 100 μM, 150 μM, and 200 μM inhibited the proliferation, migration, and invasion of SW480 cells in a time- and concentration-dependent manner. Rotundine does not induce SW480 cell apoptosis. Compared to the control group, high-throughput results showed that there were 385 DEGs in the SW480 group. And DEGs were associated with the Hippo signaling pathway. In addition, 16 of the DEGs were significantly associated with poorer prognosis in COAD, with MEF2B, CCDC187, PSD2, RGS16, PLXDC1, HELB, ASIC3, PLCH2, IGF2BP3, CLHC1, DNHD1, SACS, H1-4, ANKRD36, and ZNF117 being highly expressed in COAD and ARV1 being lowly expressed. Prognosis-related DEGs were mainly enriched in cancer-related pathways and biological functions, such as inositol phosphate metabolism, enterobactin transmembrane transporter activity, and enterobactin transport. Prognostic modeling also showed that these 16 DEGs could be used as predictors of overall survival prognosis in COAD patients. Conclusions: Rotundine inhibits the development and progression of colorectal cancer by regulating the expression of these prognosis-related genes. Our findings could further provide new directions for the treatment of colorectal cancer.