GSE167512
RNA Sequencing of three pairs of gastric cancer tissues
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. Overall design: RNA profiles of three pairs of gastric cancer and adjacent normal gastric tissues were generated with Illumina HiSeq 4000 Sequencer.