PMID- 36715854 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20240320 IS - 1573-6822 (Electronic) IS - 0742-2091 (Linking) VI - 39 IP - 6 DP - 2023 Dec TI - ZFX-mediated upregulation of CEBPA-AS1 contributes to acute myeloid leukemia progression through miR-24-3p/CTBP2 axis. PG - 2631-2645 LID - 10.1007/s10565-023-09792-y [doi] AB - Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Wang, Chengyi AU - Wang C AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Song, Chao-Min AU - Song CM AD - Department of Neonatology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Liu, Shan AU - Liu S AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Chen, Lu-Min AU - Chen LM AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Xue, Shu-Fang AU - Xue SF AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Huang, Si-Han AU - Huang SH AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Lin, Han AU - Lin H AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. AD - Fujian Children's Hospital, Fuzhou, China. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. FAU - Liu, Guang-Hua AU - Liu GH AD - Department of Pediatrics, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, China. Liugh1962815@hotmail.com. AD - Fujian Children's Hospital, Fuzhou, China. Liugh1962815@hotmail.com. AD - Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China. Liugh1962815@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230130 PL - Switzerland TA - Cell Biol Toxicol JT - Cell biology and toxicology JID - 8506639 RN - 0 (MicroRNAs) RN - 0 (Transcription Factors) RN - 0 (RNA, Long Noncoding) RN - EC 1.1.- (CTBP2 protein, human) RN - EC 1.1.- (Alcohol Oxidoreductases) RN - 0 (Co-Repressor Proteins) RN - 0 (CEBPA protein, human) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (MIRN24 microRNA, human) SB - IM MH - Humans MH - *MicroRNAs/genetics/metabolism MH - Up-Regulation/genetics MH - Cell Line, Tumor MH - In Situ Hybridization, Fluorescence MH - *Leukemia, Myeloid, Acute/genetics MH - Transcription Factors/genetics MH - *RNA, Long Noncoding/genetics/metabolism MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Cell Movement/genetics MH - Alcohol Oxidoreductases/genetics/metabolism MH - Co-Repressor Proteins/genetics/metabolism MH - CCAAT-Enhancer-Binding Proteins/genetics/metabolism OTO - NOTNLM OT - AML OT - CEBPA-AS1 OT - CTBP2 OT - ZFX OT - miR-24-3p EDAT- 2023/01/31 06:00 MHDA- 2023/12/04 12:41 CRDT- 2023/01/30 11:24 PHST- 2022/10/17 00:00 [received] PHST- 2023/01/17 00:00 [accepted] PHST- 2023/12/04 12:41 [medline] PHST- 2023/01/31 06:00 [pubmed] PHST- 2023/01/30 11:24 [entrez] AID - 10.1007/s10565-023-09792-y [pii] AID - 10.1007/s10565-023-09792-y [doi] PST - ppublish SO - Cell Biol Toxicol. 2023 Dec;39(6):2631-2645. doi: 10.1007/s10565-023-09792-y. Epub 2023 Jan 30.