The receptor for advanced glycation end-products (RAGE) is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT) were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase-2 (MMP-2) was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039), and correlated with lymph node metastases (P=0.026). Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.

Gastric cancer is one of the most common malignant tumors of the digestive system. According to the latest statistics of the World Health Organization, both the incidence and mortality rate of gastric cancer ranked seventh among all malignancies. 1 In 2020, the United States expects 27,600 new cases of gastric cancer and 11,010 deaths from gastric cancer. 1 The high incidence and mortality rate of gastric cancer make it a public health concern, especially

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (P less than 0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.

Background: The present study was targeted at investigating the effects of hsa_circRNA_0008092 (circ_0008092) on hepatocellular carcinoma (HCC) cell proliferation, migration, invasion and apoptosis, and its related mechanism. Methods: The gene expression profiles of GSE166678 were downloaded from the Gene Expression Omnibus database and differentially expressed circRNAs in human HCC were screened out. Besides, circ_0008092, microRNA-502-5p (miR-502-5p) and cyclin D1 (CCND1) expressions in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell countering kit-8 (CCK-8), Transwell and flow cytometry assays were used to detect the proliferation, migration, invasion and apoptosis of HCC cells. Bioinformatics was utilized to predict the targeted relationships between miR-502-5p and circ_0008092, as well as miR-502-5p and CCND1 mRNA 3'-untranslated region (3’UTR). Western blot assay was applied to detect CCND1 protein expression in HCC cells. Results: Circ_0008092 was highly expressed in HCC tissues and cells, which was associated with a shorter survival time in patients with HCC. Circ_0008092 overexpression promoted proliferation, migration and invasion, and inhibited apoptosis of HCC cells; circ_0008092 knockdown worked oppositely. Circ_0008092 directly targeted miR-502-5p and negatively modulated miR-502-5p expression. CCND1 was a target gene of miR-502-5p, and was positively and indirectly modulated by circ_0008092. Conclusions: Our data suggest that circ_0008092 promotes HCC progression by regulating the miR-502-5p/CCND1 axis.