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Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis, induces cell proliferation, and represses cell apoptosis via targeting aurora kinase A in adult acute myeloid leukemia

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Abstract

This study aimed to investigate the correlation of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis, and to explore its effect on cell proliferation and apoptosis as well as the relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1 expression was detected in bone marrow samples from 186 AML patients and 62 controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor lentivirus vectors were transfected in KG-1 cells. Rescue experiment was performed by transfection of lncRNA TUG1 inhibitor and aurora kinase A (AURKA) mimic lentivirus vectors. Cell proliferation, apoptosis, RNA, and protein expressions were determined by CKK-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and western blot assays. LncRNA TUG1 expression was higher in AML patients compared to controls and correlated with higher white blood cell counts, monosomal karyotype, FLT3-ITD mutation, poor-risk stratification, and poor prognosis, which independently predicted worse event-free survival and overall survival. In vitro, lncRNA TUG1 expression was higher in AML cell lines (KG-1, MOLM-14, HL-60, NB-4, and THP-1 cells) compared to controls. LncRNA TUG1 mimic promoted cell proliferation and decreased cell apoptosis rate, while lncRNA TUG1 inhibitor repressed cell proliferation and increased cell apoptosis rate. Rescue experiment showed that AURKA attenuated the influence of lncRNA TUG1 on AML cell proliferation and apoptosis. In conclusion, lncRNA TUG1 associates with advanced disease and worse prognosis in adult AML patients, and it induces AML cell proliferation and represses cell apoptosis via targeting AURKA.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81201857) and Nantong Science and Technology Project Foundation, China (No. MS12016012).

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  1. Xinfeng Wang and Lina Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China

    Xinfeng Wang, Lina Zhang, Fan Zhao, Ruirong Xu, Jie Jiang, Chenglu Zhang, Hong Liu & Hongming Huang

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  1. Xinfeng Wang
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Correspondence to Hong Liu or Hongming Huang.

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This study was performed under the Institutional Review Board approvals from The Affiliated Hospital of Nantong University Hospital and conducted in accordance with the Declaration of Helsinki. Written informed consents had been obtained from all patients and controls.

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Wang, X., Zhang, L., Zhao, F. et al. Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis, induces cell proliferation, and represses cell apoptosis via targeting aurora kinase A in adult acute myeloid leukemia. Ann Hematol 97, 1375–1389 (2018). https://doi.org/10.1007/s00277-018-3315-8

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