ABSTRACT: Stomach cancer (GC) remains one of the most prevalent tumors globally, ranking third in terms of cancer-related mortality worldwide. Currently, the prognosis for gastric cancer following radical resection is still suboptimal, primarily due to metastasis. Therefore, it is crucial to explore target therapy as a means to address this issue. Circular RNAs (circRNAs) have emerged as pivotal regulators in the development and progression of cancer and hold promise as biomarkers for diagnosing and prognosticating various cancers. However, the precise mechanism by which circular RNA contributes to metastasis in gastric cancer remains unclear. Our objective is to validate the expression profile of circRNA in gastric cancer and investigate its functional role in metastasis within this context.
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:We have performed gene expression microarray analysis to profile transcriptomic signatures between cancer and noncancerous patients Gastric cancer is currently the second leading cause of cancer deaths. Due to the difficulty of diagnosing patients in the early stages of gastric cancer, it is critical to develop a method that can diagnose the disease at the early stage to allow for better treatment options. In this study, we discovered salivary transcriptomic and miRNA biomarkers for the detection of gastric cancer and identified there are mRNA-miRNA correlations in saliva. RNA was extracted from saliva supernatant and mRNA candidates were identified that can distinguish gastric cancer from non-gastric cancer patients
Project description:By the high sensitive cricular RNA micro array, we commpared 10211 circular RNAs abundant in the human gastric cancer tissues and adjacent normal gastric mucosa tissues, and the functional role of differentially expressed circular RNAs were analyzed by bioinformatics. The enrichment results indicated that these circular RNAs may involevd in the occurrence and progression process of gastric cancer.
Project description:Gastric cancer (GC) is associated with high mortality rates and an unfavorable prognosis at advanced stages. In addition, there are no effective methods for diagnosing gastric cancer at an early stage or for predicting the outcome for the purpose of selecting patient-specific treatment options. Therefore, it is important to investigate new methods for GC diagnosis. We designed a custom microarray of gastric cancer. The customized microarray contained 1042 canceration and prognosis related genes identical to the probes on the Agilent microarray. DNA microarray profilling analysis was performed on gastric cancer tissues and premalignant tissues (20 samples per group).
Project description:Human primary gastric cancer tissue SAGE libraries. Profile of the genes expressed in well and poorly differentiated gastric cancer, early and advanced gastric cancer, scirrhous type gastric cancer, and lymph node metastasis determined through SAGE. Keywords = gastric cancer, histology, early gastric cancer, advanced gastric cancer, lymph node metastasis, scirrhous type gastric cancer Keywords: other
Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between cancer and noncancerous patients Gastric cancer is currently the second leading cause of cancer deaths. Due to the difficulty of diagnosing patients in the early stages of gastric cancer, it is critical to develop a method that can diagnose the disease at the early stage to allow for better treatment options. In this study, we discovered salivary transcriptomic and miRNA biomarkers for the detection of gastric cancer and identified there are mRNA-miRNA correlations in saliva.
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: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:Metastasis is a major problem of gastric cancer. In this study, small extracellular vesicle (sEV)-derived miRNAs were sequenced to screen biomarkers for GC’s organo-tropic metastasis. Plasma from 40 treatment-naïve gastric cancer patients including 10 no metastasis (M0) and 30 distant metastasis (M1) were assessed by sEV-miRNA-sequencing. sEV miRNAs with diverse expression profiles across different metastatic patterns were combined into sigantures to characterize and predict gastric cancer metastasis.