PMID- 37431919 OWN - NLM STAT- MEDLINE DCOM- 20231026 LR - 20231026 IS - 1098-2744 (Electronic) IS - 0899-1987 (Linking) VI - 62 IP - 11 DP - 2023 Nov TI - Circ_0001589/miR-1248/HMGB1 axis enhances EMT-mediated metastasis and cisplatin resistance in cervical cancer. PG - 1645-1658 LID - 10.1002/mc.23605 [doi] AB - Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer. CI - (c) 2023 Wiley Periodicals LLC. FAU - Ma, Teng AU - Ma T AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Guo, Jianxin AU - Guo J AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Han, Jian AU - Han J AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Li, Lanfang AU - Li L AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Ren, Yifei AU - Ren Y AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Huang, Jie AU - Huang J AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Diao, Ge AU - Diao G AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Zheng, Xiuhui AU - Zheng X AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. FAU - Zheng, Yingru AU - Zheng Y AUID- ORCID: 0000-0002-4146-7796 AD - Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230711 PL - United States TA - Mol Carcinog JT - Molecular carcinogenesis JID - 8811105 RN - 0 (3' Untranslated Regions) RN - Q20Q21Q62J (Cisplatin) RN - 0 (HMGB1 Protein) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (HMGB1 protein, human) SB - IM MH - Animals MH - Female MH - Humans MH - Mice MH - 3' Untranslated Regions MH - Carcinogenesis MH - Cell Line, Tumor MH - Cell Proliferation MH - Cisplatin/pharmacology MH - Epithelial-Mesenchymal Transition MH - *HMGB1 Protein MH - Mice, Nude MH - *MicroRNAs/genetics MH - *Rectal Neoplasms MH - RNA, Circular/genetics MH - *Uterine Cervical Neoplasms/drug therapy/genetics OTO - NOTNLM OT - cervical cancer OT - circular RNA OT - drug resistance OT - metastasis EDAT- 2023/07/11 13:10 MHDA- 2023/10/23 00:43 CRDT- 2023/07/11 08:03 PHST- 2023/05/30 00:00 [revised] PHST- 2023/03/23 00:00 [received] PHST- 2023/06/11 00:00 [accepted] PHST- 2023/10/23 00:43 [medline] PHST- 2023/07/11 13:10 [pubmed] PHST- 2023/07/11 08:03 [entrez] AID - 10.1002/mc.23605 [doi] PST - ppublish SO - Mol Carcinog. 2023 Nov;62(11):1645-1658. doi: 10.1002/mc.23605. Epub 2023 Jul 11.