PMID- 38092323 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20240201 IS - 1089-8646 (Electronic) IS - 0888-7543 (Linking) VI - 116 IP - 1 DP - 2024 Jan TI - A novel link between circPDE3B and ferroptosis in esophageal squamous cell carcinoma progression. PG - 110761 LID - S0888-7543(23)00205-7 [pii] LID - 10.1016/j.ygeno.2023.110761 [doi] AB - AIM: To unravel whether ferroptosis involves with the actions by circPDE3B-mediated facilitation of esophageal squamous cell carcinoma (ESCC) progression. METHODS: Human ESCC tissues and cell lines were prepared for the evaluation of ferroptosis. Cellular iron, ROS, GSH, and MDA levels were measured to assess ferroptosis. Flow cytometry was employed to analyze apoptosis and cell cycle. Subcellular fractionation and fluorescence in situ hybridization (FISH) were conducted to validate the localization of circPDE3B. RNA pull-down, RNA immunoprecipitation (RIP), and luciferase assay were subjected to identify the molecular mechanisms. Nude mouse xenograft model was carried out to evaluate the function of circPDE3B/SLC7A11/CBS in vivo. RESULTS: Increased circPDE3B in human ESCC specimens was positively correlated with ferroptosis-related molecules, SLC7A11 and CBS. Functionally, circPDE3B knockdown triggered ferroptosis, apoptosis, and cell cycle arrest in ESCC cells. Whereas, these effects were obviously blocked by miR-516b-5p inhibitor. Mechanistically, not only circPDE3B sponged miR-516b-5p to upregulate CBS, but also directly bound with HNRNPK to stabilize SLC7A11. In mice, depletion of circPDE3B restrained ESCC growth, while this was abolished by overexpression of CBS or SLC7A11. CONCLUSION: In summary, circPDE3B promotes ESCC progression by suppressing ferroptosis through recruiting HNRNPK/SLC7A11 and miR-516b-5p/CBS axes. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Zhou, Pengli AU - Zhou P AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. FAU - Wu, Zhengyang AU - Wu Z AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. FAU - Zhang, Qinghui AU - Zhang Q AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. FAU - Wang, Ling AU - Wang L AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. FAU - Zhang, Wenguang AU - Zhang W AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. FAU - Han, Xinwei AU - Han X AD - Intervention Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, PR China. Electronic address: hanxinwei2006@163.com. LA - eng PT - Journal Article DEP - 20231211 PL - United States TA - Genomics JT - Genomics JID - 8800135 RN - 0 (MicroRNAs) SB - IM MH - Humans MH - Animals MH - Mice MH - *Esophageal Squamous Cell Carcinoma/pathology MH - *Esophageal Neoplasms/pathology MH - *MicroRNAs/genetics/metabolism MH - *Ferroptosis/genetics MH - In Situ Hybridization, Fluorescence MH - Cell Proliferation/genetics MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic OTO - NOTNLM OT - CBS OT - CircPDE3B OT - Esophageal squamous cell carcinoma OT - Ferroptosis OT - HNRNPK OT - MiR-516b-5p OT - SLC7A11 COIS- Declaration of Competing Interest The authors declare no competing financial interests. EDAT- 2023/12/14 00:42 MHDA- 2024/01/22 06:41 CRDT- 2023/12/13 19:29 PHST- 2023/07/14 00:00 [received] PHST- 2023/10/30 00:00 [revised] PHST- 2023/12/10 00:00 [accepted] PHST- 2024/01/22 06:41 [medline] PHST- 2023/12/14 00:42 [pubmed] PHST- 2023/12/13 19:29 [entrez] AID - S0888-7543(23)00205-7 [pii] AID - 10.1016/j.ygeno.2023.110761 [doi] PST - ppublish SO - Genomics. 2024 Jan;116(1):110761. doi: 10.1016/j.ygeno.2023.110761. Epub 2023 Dec 11.