Project description:Circular (circ) RNAs have been widely reported to be involved in gastric cancer (GC) pathogenesis and coiled coil domain containing 6 (CCDC6) is recognized as fused partner of multiple oncogenes; however, the underlying mechanisms of how circRNAs regulate CCDC6 expression in the progression and prognosis of GC remain unclear. Here, we discovered a novel circRNA derived from the DNA2 gene locus (circDNA2) through joint analysis of circRNA microarrays. By performing qRT-PCR and FISH assays with a human tissue microarray, circDNA2 was identified to be highly expressed in GC tissues and associated with lymphatic invasion of GC patients. Knockdown of circDNA2 suppressed the proliferation of GC cells by reducing CCDC6 expression in vitro. Mechanically, circDNA2 acted as a sponge for microRNA (miR)-149-5p, which was validated to target CCDC6 by dual luciferase reporter assays and rescue experiments. Both miR-149-5p low expression and CCDC6 high expression were related to unfavorable prognosis of GC patients. Moreover, GC patients with low miR-149-5p expression had shorter overall survival and higher risk of chemotherapy resistance compared with these with high miR-149-5p expression. In summary, our findings reveal that circDNA2 contributes to the growth and lymphatic metastasis of GC through upregulating CCDC6 expression via sponging miR-149-5p. The circDNA2/miR-149-5p/CCDC6 axis might be developed as a therapeutic target and prognostic indicator for GC patients.
Project description:The prognosis after curative resection of gastric cancer (GC) remains unsatisfactory, and thus, the development of treatments involving alternative molecular and genetic targets is critical. Circular RNAs (circRNAs), new stars of the non-coding RNA network, have been identified as critical regulators in various cancers. Here, we aimed to determine the circRNA expression profile and investigate the functional and prognostic significance of circRNA in GC. Using next-generation sequencing profiling, we first characterized an abundant circRNA, hsa_circ_0008549, derived from the OSBPL10 gene, and named it circOSBPL10. The expression of circOSBPL10 was found via quantitative real-time RT-PCR (qRT-PCR) to be upregulated in GC tissues, and silencing of circOSBPL10 significantly inhibited gastric cancer cell growth, migration and invasion in multiple experiments. We further confirmed that miR-136-5p is a downstream target of circOSBPL10 using RNA pull-down and luciferase reporter assays. Rescue experiments confirmed that circOSBPL10 regulates biological functions in GC cells via a circOSBPL10-miR-136-5p-WNT2 axis. In vivo experiments showed that circOSBPL10 promotes tumor growth and metastasis in mice. Furthermore, the level of circOSBPL10 was observed to be a prognostic marker of the overall survival and disease-free survival of patients with GC. Taken together, our findings reveal that circOSBPL10 may serve as a new proliferation factor and prognostic marker in gastric cancer.
Project description:Methylated modifications of genome are common events in carcinogenesis and is involved in the tumorigenesis and progression of various cancers including gastric cancer Methylated DNA immunoprecipitation (MeDIP) combined with a human miRNA tiling microarray analysis demonstrated that there are much methylation differention between gastric cancers and adjacent controls microRNA gene methylation comparison of 3 pairs of gastric cancer and controls
Project description:The goal of the project is to analyze different layers of proteome information including protein abundance and post-translational modifications of PGRC gastric tissue samples. Three pairs of human gastric cancer and adjacent normal tissues were extensively characterized by serial enrichments of phosphorylation and N-glycosylation (SEPG) coupled to LC-MS/MS method.
Project description:To elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues. 25 pairs of gastric tissues: gastric cancer tissues vs. matched adjacent noncancerous tissues.
Project description:The goal of the project is to analyze different layers of proteome information including protein abundance and post-translational modifications of PGRC gastric tissue samples. Three pairs of human gastric cancer and adjacent normal tissues were extensively characterized by serial enrichments of phosphorylation and N-glycosylation (SEPG) coupled to LC-MS/MS method.
Project description:Copy number variation profiling of gastric tissues comparing gastric cancer tissues with matched adjacent noncancerous tissues. Goal was to determine the effects of chromosomal imbalances on gene expression and carcinogenesis or progression. 27 pairs of gastric tissues: gastric cancer tissues vs. matched adjacent noncancerous tissues.
Project description:Gastric cancer is one of the most common malignant tumors. Asia has a high incidence of gastric cancer globally. South Korea, Mongolia, Japan and China are the four countries with the highest incidence of gastric cancer in the world. Gansu province in China has the estimated age-standardized incidence rates and mortality rates by Chinese standard population of 62.34/100,000 and 36.94/100,000, respectively, in 2012, which are much higher than the average level of China (22.06/100,000 and 15.16/100,000) in the same year. As a high incidence area of gastric cancer in China, Wuwei city in Gansu province has the prevalence of gastric cancer almost 5 times higher than the average level nationwide. In this study, the cancer tissues and matched adjacent normal mucosa tissues of 5 patients with early gastric cancers who were treated with ESD in Gansu Wuwei Tumor Hospital and the First Hospital of Lanzhou University were collected. All of the patients are from Gansu, China. MicroRNA array was used to find the differences in microRNAs expression profile between the early gastric cancer tissues and the para-cancer normal tissues. It is expected to explore the reasons of the abnormal high incidence of gastric cancer in Gansu Province, China, from the aspect of microRNAs expression profile characteristics.