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RNA Sequencing of three pairs of gastric cancer

ABSTRACT: RNA Sequencing of three pairs of gastric cancer

PROVIDER: PRJNA506381 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8233761_1.fastq.gz	Fastqsanger.gz
	SRR8233761_2.fastq.gz	Fastqsanger.gz
	SRR8233762_1.fastq.gz	Fastqsanger.gz
	SRR8233762_2.fastq.gz	Fastqsanger.gz
	SRR8233763_1.fastq.gz	Fastqsanger.gz

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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.

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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.

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