PMID- 35518784 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1687-8450 (Print) IS - 1687-8469 (Electronic) IS - 1687-8450 (Linking) VI - 2022 DP - 2022 TI - LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer through MBNL1-AS1/ZFP36/CENPA Axis. PG - 9999343 LID - 10.1155/2022/9999343 [doi] LID - 9999343 AB - BACKGROUND: Emerging studies have revealed long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast cancer (BC). METHODS: In this study, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line, was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, extreme limiting dilution analysis (ELDA), fluorescence in situ hybridization (FISH), flow cytometry assays, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and FISH were conducted to detect the mechanism. RESULTS: The results showed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. CONCLUSIONS: The new mechanism of how MBNL1-AS1 regulates BC phenotype is elucidated, and the MBNL1-AS1/ZFP36/CENPA axis may be served as a therapeutic target for BC patients. CI - Copyright (c) 2022 Yu Ding et al. FAU - Ding, Yu AU - Ding Y AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Li, Yingjie AU - Li Y AD - Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Duan, Yunqiang AU - Duan Y AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wang, Wan AU - Wang W AD - Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, China. FAU - Zheng, Wei AU - Zheng W AD - Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Cheng, Weilun AU - Cheng W AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Qi, Yuan AU - Qi Y AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Feng, Jianyuan AU - Feng J AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Chen, Ziang AU - Chen Z AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Yu, Tianshui AU - Yu T AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Hu, Anbang AU - Hu A AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wang, Ting AU - Wang T AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Li, Mingcui AU - Li M AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Zhang, Hanyu AU - Zhang H AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Li, Yanling AU - Li Y AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Ma, Fei AU - Ma F AUID- ORCID: 0000-0002-7068-8846 AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Guo, Baoliang AU - Guo B AUID- ORCID: 0000-0002-4022-6739 AD - Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. LA - eng PT - Journal Article DEP - 20220426 PL - Egypt TA - J Oncol JT - Journal of oncology JID - 101496537 PMC - PMC9064507 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/05/07 06:00 MHDA- 2022/05/07 06:01 PMCR- 2022/04/26 CRDT- 2022/05/06 06:00 PHST- 2021/10/19 00:00 [received] PHST- 2022/03/12 00:00 [revised] PHST- 2022/03/30 00:00 [accepted] PHST- 2022/05/06 06:00 [entrez] PHST- 2022/05/07 06:00 [pubmed] PHST- 2022/05/07 06:01 [medline] PHST- 2022/04/26 00:00 [pmc-release] AID - 10.1155/2022/9999343 [doi] PST - epublish SO - J Oncol. 2022 Apr 26;2022:9999343. doi: 10.1155/2022/9999343. eCollection 2022.