Circ_0067997 boosted the growth while repressed the apoptosis of SGC-7901/DDP cells via repressing miR-615-5p/AKT1 pathway.

BACKGROUND: Gastric cancer (GC) remains a huge challenge to the heathy of human beings, largely due to lacking of effective therapeutic measures. Though an oncogenic role for circular RNAs (circRNAs) circ_0067997 in the progression of GC has been described recently, the molecular modulatory mechanism of it still remains to be further explored. The aim of present study is to examine the molecular network of circ_0067997 in GC. METHODS: qRT-PCR was carried out to determine the mRNA levels of circ_0067997, miR-615-5p and AKT1 in cisplatin (DDP)-insensitive or sensitive GC tumor tissues and cells, while the correlations among the contents of these molecules were determined by statistical analysis. The expression of circ_0067997 was manipulated by short-hairpin RNA and lentiviral-mediated approaches, while that of miR-615-5p was achieved by the application of its inhibitor or mimic. The in vivo action of circ_0067997 on tumor formation was determined by measuring tumor weight/volume/size and analyzing tumor apoptosis through TUNEL staining in mouse xenograft model and, while the in vitro effects of this circRNA and its target miR-615-5p on the cell survival and death were separately evaluated by CCK-8 assay and flow cytometry. Additionally, luciferase reporter assays were executed to determine the sequentially regulatory relationships of circ_0067997, miR-615-5p, and AKT1. RESULTS: Our data demonstrated that the level of circ_0067997 level was increased in DDP-insensitive GC tissues and cell line, while miR-615-5p presented the opposite results. Moreover, the relationships between circ_0067997 and miR-615-5p levels, circ_0067997 and AKT1 contents presented negative and positive correlations in clinic samples, respectively. Importantly, circ_0067997 was found to repress miR-615-5p expression, consequently leading to increased growth while reduced apoptosis of GC cells in the presence of DDP. Furthermore, the validated sequential regulation was circ_0067997 modulating miR-615-5p adjusting AKT1. CONCLUSIONS: This study demonstrated that circ_0067997 functioned as a sponge of miR-615-5p to target AKT1 expression, thereby enhancing the growth and restricting the apoptosis of DDP-insensitive GC cells. These new findings offered a valuable target for the detection and management of GC.

Development of a prognostic metabolic signature in stomach adenocarcinoma

PurposeThe growth and aggressiveness of Stomach adenocarcinoma (STAD) is significantly affected by basic metabolic changes. This study aimed to identify metabolic gene prognostic signatures in STAD.MethodsAn integrative analysis of datasets from the Cancer Genome Atlas and Gene Expression Omnibus was performed. A metabolic gene prognostic signature was developed using univariable Cox regression and Kaplan–Meier survival analysis. A nomogram model was developed to predict the prognosis of STAD patients. Finally, Gene Set Enrichment Analysis (GESA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways significantly associated with the risk grouping.ResultsA total of 327 metabolism-related differentially expressed genes were identified. Three subtypes of STAD were identified and nine immune cell types, including memory B cell, resting and activated CD4+ memory T cells, were significantly different among the three subgroups. A risk score model including nine survival-related genes which could separate high-risk patients from low-risk patients was developed. The prognosis of STAD patients likely benefited from lower expression levels of genes, including ABCG4, ABCA6, GPX8, KYNU, ST8SIA5, and CYP19A1. Age, radiation therapy, tumor recurrence, and risk score model status were found to be independent risk factors for STAD and were used for developing a nomogram. Nine KEGG pathways, including spliceosome, pentose phosphate pathway, and citrate TCA cycle were significantly enriched in GESA.ConclusionWe propose a metabolic gene signature and a nomogram for STAD which might be used for predicting the survival of STAD patients and exploring prognostic markers. (AU)

Development of a prognostic metabolic signature in stomach adenocarcinoma.

PURPOSE: The growth and aggressiveness of Stomach adenocarcinoma (STAD) is significantly affected by basic metabolic changes. This study aimed to identify metabolic gene prognostic signatures in STAD. METHODS: An integrative analysis of datasets from the Cancer Genome Atlas and Gene Expression Omnibus was performed. A metabolic gene prognostic signature was developed using univariable Cox regression and Kaplan-Meier survival analysis. A nomogram model was developed to predict the prognosis of STAD patients. Finally, Gene Set Enrichment Analysis (GESA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways significantly associated with the risk grouping. RESULTS: A total of 327 metabolism-related differentially expressed genes were identified. Three subtypes of STAD were identified and nine immune cell types, including memory B cell, resting and activated CD4+ memory T cells, were significantly different among the three subgroups. A risk score model including nine survival-related genes which could separate high-risk patients from low-risk patients was developed. The prognosis of STAD patients likely benefited from lower expression levels of genes, including ABCG4, ABCA6, GPX8, KYNU, ST8SIA5, and CYP19A1. Age, radiation therapy, tumor recurrence, and risk score model status were found to be independent risk factors for STAD and were used for developing a nomogram. Nine KEGG pathways, including spliceosome, pentose phosphate pathway, and citrate TCA cycle were significantly enriched in GESA. CONCLUSION: We propose a metabolic gene signature and a nomogram for STAD which might be used for predicting the survival of STAD patients and exploring prognostic markers.