Prognostic significance of JAM 3 in gastric cancer: An observational study from TCGA and GEO.

Junctional adhesion molecule 3 (JAM3) can be used as a prognostic marker in multiple cancer types. However, the potential prognostic role of JAM3 in gastric cancer (GC) remains unclear. The purpose of this research was to gauge JAM3 expression and methylation as potential biomarkers for GC patient survival. Through bioinformatics research, we analyzed JAM3 expression, methylation, prognosis, and immune cell infiltrations. JAM3 methylation acts as a negative regulator of JAM3, leading to reduced expression of JAM3 in GC tissues relative to normal tissues. Patients with GC who expressed little JAM3 have a better chance of living a long time free of the disease, according to the Cancer Genome Atlas (TCGA) database. Through univariate and multivariate Cox regression analysis, inadequate JAM3 expression was labeled as an isolated indicator for overall survival (OS). The GSE84437 dataset was also used to confirm JAM3 prognostic role in GC, with consistent findings. A meta-analysis also found that low levels of JAM3 expression were significantly associated with longer OS. Finally, there was a strong correlation between JAM3 expression and a subset of immune cells. According to the TCGA database, low JAM3 expression could predict favorable OS and progression-free-survival (PFS) in GC patients (P < .05). The univariate and multivariate Cox regression demonstrated that low JAM3 expression was independent biomarker for OS (P < .05). Moreover, GSE84437 dataset was utilized to verify the prognostic role of JAM3 in GC, and the similar results were reached (P < .05). A meta-analysis revealed that low JAM3 expression was closely relevant to better OS. Finally, JAM3 expression exhibited a close correlation with some immune cells (P < .05). JAM3 might be a viable predictive biomarker and likely plays a crucial part in immune cell infiltration in individuals with GC.

LncRNA BDNF-AS suppresses colorectal cancer cell proliferation and migration by epigenetically repressing GSK-3ß expression.

This study was designed to investigate the molecular mechanism and biological roles of long non-coding RNA (lncRNA) brain-derived neurotrophic factor antisense (BDNF-AS) in colorectal cancer (CRC). The quantitative real-time PCR (qRT-PCR) and western blotting were performed to detect the expressions of lncRNA BDNF-AS and glycogen synthase kinase-3ß (GSK-3ß) in human CRC tissues and cell lines. The cell proliferation, transwell migration, and invasion assays were carried out to evaluate the effect of lncRNA BDNF-AS on the growth of CRC cells. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to confirm the interaction between lncRNA BDNF-AS and enhancer of Zeste Homologue 2 (EZH2). Chromatin immunoprecipitation (ChIP) assay was used to verify the enrichment of EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) in the promoter region of GSK-3ß in CRC cells. LncRNA BDNF-AS expression was significantly decreased, while GSK-3ß was highly expressed in human CRC tissues and cell lines. Moreover, lncRNA BDNF-AS induced inhibition of proliferation, migration, and invasion of CRC cells via inhibiting GSK-3ß expression. Mechanistically, BDNF-AS led to GSK-3ß promoter silencing in CRC cells through recruitment of EZH2. In conclusion, lncRNA BDNF-AS functioned as an oncogene in CRC and shed new light on lncRNA-directed therapeutics in CRC. SIGNIFICANCE OF THE STUDY: LncRNA BDNF-AS is recently reported to be remarkably downregulated in a variety of tumours and served as a tumour suppressor. However, the functions and underlying mechanism of lncRNA BDNF-AS in CRC pathogenesis have not been reported yet. Our study is the first to demonstrate the effect of lncRNA BDNF-AS in CRC and revealed that lncRNA BDNF-AS expression is negatively correlated with the aggressive biological behaviour of CRC. Further investigation demonstrated that lncRNA BDNF-AS functioned as a tumour suppressor in CRC progression by suppressing GSK-3ß expression through binding to EZH2 and H3K27me3 with the GSK-3ß promoter, shedding light on the diagnosis and therapy for CRC.