PMID- 34419070 OWN - NLM STAT- MEDLINE DCOM- 20220124 LR - 20240102 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 20 IP - 1 DP - 2021 Aug 21 TI - Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis. PG - 106 LID - 10.1186/s12943-021-01400-z [doi] LID - 106 AB - BACKGROUND: Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. METHODS: CircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294. RESULTS: CircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions. CONCLUSION: CircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC. CI - (c) 2021. The Author(s). FAU - Rong, Zeyin AU - Rong Z AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Shi, Si AU - Shi S AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Tan, Zhen AU - Tan Z AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Xu, Jin AU - Xu J AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Meng, Qingcai AU - Meng Q AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Hua, Jie AU - Hua J AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Liu, Jiang AU - Liu J AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Zhang, Bo AU - Zhang B AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Wang, Wei AU - Wang W AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. FAU - Yu, Xianjun AU - Yu X AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. yuxianjun@fudanpci.org. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. yuxianjun@fudanpci.org. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. yuxianjun@fudanpci.org. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. yuxianjun@fudanpci.org. FAU - Liang, Chen AU - Liang C AUID- ORCID: 0000-0003-0578-7589 AD - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, PR China. liangchen@fudanpci.org. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. liangchen@fudanpci.org. AD - Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. liangchen@fudanpci.org. AD - Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. liangchen@fudanpci.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210821 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (DNA-Binding Proteins) RN - 0 (MIRN1294 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 3.1.3.48 (EYA3 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Adult MH - Aged MH - Apoptosis/genetics MH - Carcinoma, Pancreatic Ductal/*genetics/*metabolism/pathology MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation MH - DNA-Binding Proteins/*genetics MH - *Energy Metabolism MH - Female MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Humans MH - Male MH - MicroRNAs/genetics MH - Middle Aged MH - Models, Biological MH - Neoplasm Grading MH - Neoplasm Staging MH - Pancreatic Neoplasms/*genetics/*metabolism/pathology MH - Prognosis MH - Protein Tyrosine Phosphatases/*genetics MH - RNA Interference MH - *RNA, Circular PMC - PMC8379744 OTO - NOTNLM OT - ATP production OT - C-Myc OT - CircEYA3 OT - Pancreatic ductal adenocarcinoma OT - miR-1294 COIS- The authors declare no conflict of interest. EDAT- 2021/08/23 06:00 MHDA- 2022/01/27 06:00 PMCR- 2021/08/21 CRDT- 2021/08/22 20:28 PHST- 2021/06/16 00:00 [received] PHST- 2021/08/03 00:00 [accepted] PHST- 2021/08/22 20:28 [entrez] PHST- 2021/08/23 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/08/21 00:00 [pmc-release] AID - 10.1186/s12943-021-01400-z [pii] AID - 1400 [pii] AID - 10.1186/s12943-021-01400-z [doi] PST - epublish SO - Mol Cancer. 2021 Aug 21;20(1):106. doi: 10.1186/s12943-021-01400-z.