Abstract
Background: Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. However, their roles in gastric cancer (GC) remain unclear.Methods: We analyzed the differential expressions of TFs and, using GC cells and tissues, investigated plexin C1 (PLXNC1) RNA levels, as well as PLXNC1's clinical relevance and functional mechanisms. The molecular function of PLXNC1 was evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS).Results: PLXNC1 was frequently up-regulated in GC and associated with poor prognosis. The expression level of PLXNC1 could serve as an independent biomarker to predict a patient's overall survival. Notably, knockdown of PLXNC1 significantly abolished GC cell proliferation, and migration, and overexpression of PLXNC1 accelerated carcinogenesis in GC. The gene set enrichment analysis (GSEA) indicated that high-expression of PLXNC1 was positively correlated with the activation of epithelial-mesenchymal transition (EMT), TNF-α, and IL-6/STAT3 signaling pathways. PLXNC1 promoted proliferation and migration of GC cells through transcriptional activation of the interleukin 6 signal transducer (IL6ST), which could rescue the malignant behavior of PLXNC1-deficient GC cells.Conclusions: Our study demonstrated that the PLXNC1 plays an oncogenic role in GC patients. The PLXNC1-IL6ST axis represents a novel potential therapeutic target for GC.
Highlights
Gastric cancer (GC) is one of the most malignant and prevalent tumors, with poor prognosis worldwide [1, 2]
The results showed that 372 Transcriptional factors (TFs) were highly expressed in GC compared with para-cancerous samples, whereas 63 TFs were down-regulated in tumor tissues (FDR < 0.05, fold change > 1.3; Figure 1A; Table S3)
The samples were classified into two groups according to their optimal survival cut-off point for each TF, and the difference of accumulated survival curve was represented by Kaplan-Meier analysis
Summary
Gastric cancer (GC) is one of the most malignant and prevalent tumors, with poor prognosis worldwide [1, 2]. Clinical therapeutic methods and medical technology have improved (surgical resection and target drug therapy, for example), the 5 year survival rates of GC still remain dismal [3]. Genomic technology has become the essential methodology used by international organizations to discover the novel therapeutic targets in GC [4, 5]. The Cancer Genome Atlas (TCGA) has carried out a systematic and multidimensional repertoire of genomic dysregulations, including gene expression, PLXNC1 Increases Gastric Cancer Progression gene-level-mutation, copy number variation, and clinical information for stomach adenocarcinoma (STAD). Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. Their roles in gastric cancer (GC) remain unclear
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