PMID- 37041721 OWN - NLM STAT- MEDLINE DCOM- 20230607 LR - 20240102 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 12 IP - 10 DP - 2023 May TI - CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis. PG - 11651-11671 LID - 10.1002/cam4.5869 [doi] AB - BACKGROUND: Growing evidences suggest that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell, and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion, and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft model was constructed for in vivo experiment. RESULTS: CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promotes the progression of PDAC. CONCLUSIONS: This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC. CI - (c) 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Fu, Wen AU - Fu W AUID- ORCID: 0000-0002-9724-2756 AD - Chongqing Medical University, Chongqing, 400016, China. AD - Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400174, China. AD - Chongqing School, University of Chinese Academy of Sciences, Chongqing, 400013, China. AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. FAU - Wang, Xianxing AU - Wang X AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. FAU - Xiang, Jifeng AU - Xiang J AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. FAU - Chen, Shengkai AU - Chen S AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. FAU - Xia, Renpei AU - Xia R AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. FAU - Xie, Fuming AU - Xie F AD - Chongqing Medical University, Chongqing, 400016, China. FAU - Chi, Bojing AU - Chi B AD - Chinese Academy of Sciences, Beijing, 101400, China. FAU - Qin, Fanbo AU - Qin F AD - Chongqing Medical University, Chongqing, 400016, China. FAU - Li, Zhuo AU - Li Z AD - Chinese Academy of Sciences, Beijing, 101400, China. FAU - Mou, Li AU - Mou L AD - NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China. FAU - Xie, Chuanming AU - Xie C AD - Key Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. FAU - Wang, Huaizhi AU - Wang H AD - Chongqing Medical University, Chongqing, 400016, China. AD - Department of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, 401147, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230411 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (Mirn140 microRNA, human) SB - IM MH - Humans MH - *MicroRNAs/genetics/metabolism MH - RNA, Circular/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - *Pancreatic Neoplasms/pathology MH - *Carcinoma, Pancreatic Ductal/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic MH - Cell Movement/genetics PMC - PMC10242365 OTO - NOTNLM OT - CircPTPRA OT - LMNB1 OT - MiR-140-5p OT - epithelial-mesenchymal transition OT - pancreatic ductal adenocarcinoma EDAT- 2023/04/13 06:00 MHDA- 2023/06/07 06:42 PMCR- 2023/04/11 CRDT- 2023/04/12 01:13 PHST- 2023/03/01 00:00 [revised] PHST- 2022/11/16 00:00 [received] PHST- 2023/03/16 00:00 [accepted] PHST- 2023/06/07 06:42 [medline] PHST- 2023/04/13 06:00 [pubmed] PHST- 2023/04/12 01:13 [entrez] PHST- 2023/04/11 00:00 [pmc-release] AID - CAM45869 [pii] AID - 10.1002/cam4.5869 [doi] PST - ppublish SO - Cancer Med. 2023 May;12(10):11651-11671. doi: 10.1002/cam4.5869. Epub 2023 Apr 11.