PMID- 34552818 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210925 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 26 DP - 2021 Dec 3 TI - Circular RNA circDNA2 upregulates CCDC6 expression to promote the progression of gastric cancer via miR-149-5p suppression. PG - 360-373 LID - 10.1016/j.omtn.2021.05.021 [doi] AB - Circular (circ)RNAs are widely involved in gastric cancer (GC) pathogenesis, and coiled-coil domain containing 6 (CCDC6) is a 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 the circRNA derived from the DNA2 gene locus (circDNA2) through RNA sequencing. By performing quantitative real-time PCR and fluorescence in situ hybridization (FISH) assays with a human tissue microarray, circDNA2 was found to be highly expressed in GC tissues and associated with lymphatic invasion of GC patients. Knockdown of circDNA2 expression suppressed the proliferation of GC cells by reducing CCDC6 expression. Mechanistically, circDNA2 acted as a microRNA (miR)-149-5p sponge, which was confirmed to target CCDC6 by RNA pulldown and dual-luciferase reporter assays and rescue experiments. Both low miR-149-5p expression and high CCDC6 expression were related to unfavorable prognosis in GC patients. Moreover, GC patients with low miR-149-5p expression had shorter overall survival and a higher risk of chemotherapy resistance than those with high miR-149-5p expression. In summary, circDNA2 contributes to the growth and lymphatic metastasis of GC by upregulating CCDC6 expression by sponging miR-149-5p. The circDNA2/miR-149-5p/CCDC6 axis might be developed as a therapeutic target and prognostic indicator for GC. CI - (c) 2021 The Authors. FAU - Jin, Duochen AU - Jin D AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Huang, Keting AU - Huang K AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Peng, Lei AU - Peng L AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. FAU - Xu, Ping AU - Xu P AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. FAU - Dang, Yini AU - Dang Y AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. FAU - Yang, Jiajia AU - Yang J AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. FAU - Chen, Meihong AU - Chen M AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. FAU - Zhu, Xudong AU - Zhu X AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Wei, Shuchun AU - Wei S AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Yan, Jin AU - Yan J AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Zhang, Guoxin AU - Zhang G AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China. AD - First Clinical Medical College of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20210601 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC8426470 OTO - NOTNLM OT - CCDC6 OT - circular RNA circDNA2 OT - gastric cancer OT - miR-149-5p OT - overall survival COIS- The authors declare no competing interests. EDAT- 2021/09/24 06:00 MHDA- 2021/09/24 06:01 PMCR- 2021/06/01 CRDT- 2021/09/23 06:52 PHST- 2020/11/11 00:00 [received] PHST- 2021/05/26 00:00 [accepted] PHST- 2021/09/23 06:52 [entrez] PHST- 2021/09/24 06:00 [pubmed] PHST- 2021/09/24 06:01 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - S2162-2531(21)00137-2 [pii] AID - 10.1016/j.omtn.2021.05.021 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2021 Jun 1;26:360-373. doi: 10.1016/j.omtn.2021.05.021. eCollection 2021 Dec 3.