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01-08-2018 | Original Article

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

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

Published in: Annals of Hematology | Issue 8/2018

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.

Dohner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. N Engl J Med 373(12):1136–1152. https://doi.org/10.1056/NEJMra1406184 CrossRefPubMed

Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30. https://doi.org/10.3322/caac.21387 CrossRefPubMed

Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482(7385):339–346. https://doi.org/10.1038/nature10887 CrossRefPubMedPubMedCentral

Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigo R, Gingeras TR (2012) Landscape of transcription in human cells. Nature 489(7414):101–108. https://doi.org/10.1038/nature11233 CrossRefPubMedPubMedCentral

Qiu MT, Hu JW, Yin R, Xu L (2013) Long noncoding RNA: an emerging paradigm of cancer research. Tumour Biol 34(2):613–620. https://doi.org/10.1007/s13277-013-0658-6 CrossRefPubMed

Wang L, Zhao Z, Feng W, Ye Z, Dai W, Zhang C, Peng J, Wu K (2016) Long non-coding RNA TUG1 promotes colorectal cancer metastasis via EMT pathway. Oncotarget 7(32):51713–51719. https://doi.org/10.18632/oncotarget.10563 PubMedPubMedCentralCrossRef

Liu L, Chen X, Zhang Y, Hu Y, Shen X, Zhu W (2017) Long non-coding RNA TUG1 promotes endometrial cancer development via inhibiting miR-299 and miR-34a-5p. Oncotarget 8(19):31386–31394. https://doi.org/10.18632/oncotarget.15607 PubMedPubMedCentralCrossRef

Wang PQ, Wu YX, Zhong XD, Liu B, Qiao G (2017) Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma. Eur Rev Med Pharmacol Sci 21(1):82–86PubMed

Li T, Liu Y, Xiao H, Xu G (2017) Long non-coding RNA TUG1 promotes cell proliferation and metastasis in human breast cancer. Breast Cancer 24(4):535–543. https://doi.org/10.1007/s12282-016-0736-x CrossRefPubMed

10.

Zhai HY, Sui MH, Yu X, Qu Z, Hu JC, Sun HQ, Zheng HT, Zhou K, Jiang LX (2016) Overexpression of long non-coding RNA TUG1 promotes colon cancer progression. Med Sci Monit 22:3281–3287CrossRefPubMedPubMedCentral

11.

Wenzel A, Akbasli E, Gorodkin J (2012) RIsearch: fast RNA-RNA interaction search using a simplified nearest-neighbor energy model. Bioinformatics 28(21):2738–2746. https://doi.org/10.1093/bioinformatics/bts519 CrossRefPubMedPubMedCentral

12.

Tafer H, Hofacker IL (2008) RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics 24(22):2657–2663. https://doi.org/10.1093/bioinformatics/btn193 CrossRefPubMed

13.

Li J, Ma W, Zeng P, Wang J, Geng B, Yang J, Cui Q (2015) LncTar: a tool for predicting the RNA targets of long noncoding RNAs. Brief Bioinform 16(5):806–812. https://doi.org/10.1093/bib/bbu048 CrossRefPubMed

14.

Pinero J, Bravo A, Queralt-Rosinach N, Gutierrez-Sacristan A, Deu-Pons J, Centeno E, Garcia-Garcia J, Sanz F, Furlong LI (2017) DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 45(D1):D833–D839. https://doi.org/10.1093/nar/gkw943 CrossRefPubMed

15.

Estey E, Dohner H (2006) Acute myeloid leukaemia. Lancet 368(9550):1894–1907. https://doi.org/10.1016/S0140-6736(06)69780-8 CrossRefPubMed

16.

Pan JQ, Zhang YQ, Wang JH, Xu P, Wang W (2017) lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia. Int J Mol Med. https://doi.org/10.3892/ijmm.2017.2888

17.

Hirano T, Yoshikawa R, Harada H, Harada Y, Ishida A, Yamazaki T (2015) Long noncoding RNA, CCDC26, controls myeloid leukemia cell growth through regulation of KIT expression. Mol Cancer 14:90. https://doi.org/10.1186/s12943-015-0364-7 CrossRefPubMedPubMedCentral

18.

Ou C, Li G (2017) Long non-coding RNA TUG1: a novel therapeutic target in small cell lung cancer. J Thorac Dis 9(7):E644–E645. https://doi.org/10.21037/jtd.2017.06.94 CrossRefPubMedPubMedCentral

19.

Iliev R, Kleinova R, Juracek J, Dolezel J, Ozanova Z, Fedorko M, Pacik D, Svoboda M, Stanik M, Slaby O (2016) Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer. Tumour Biol 37(10):13385–13390. https://doi.org/10.1007/s13277-016-5177-9 CrossRefPubMed

20.

Zhang E, He X, Yin D, Han L, Qiu M, Xu T, Xia R, Xu L, Yin R, De W (2016) Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57. Cell Death Dis 7:e2109. https://doi.org/10.1038/cddis.2015.356 CrossRefPubMedPubMedCentral

21.

Sun J, Ding C, Yang Z, Liu T, Zhang X, Zhao C, Wang J (2016) The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition. J Transl Med 14:42. https://doi.org/10.1186/s12967-016-0786-z CrossRefPubMedPubMedCentral

22.

Zeng B, Ye H, Chen J, Cheng D, Cai C, Chen G, Chen X, Xin H, Tang C, Zeng J (2017) LncRNA TUG1 sponges miR-145 to promote cancer progression and regulate glutamine metabolism via Sirt3/GDH axis. Oncotarget 8(69):113650–113661. https://doi.org/10.18632/oncotarget.21922 PubMedPubMedCentralCrossRef

23.

Guo P, Zhang G, Meng J, He Q, Li Z, Guan Y (2018) Upregulation of long non-coding RNA TUG1 promotes bladder cancer cell 5 proliferation, migration and invasion by inhibiting miR-29c. Oncol Res. https://doi.org/10.3727/096504018X15152085755247

24.

Fang T, Huang H, Li X, Liao J, Yang Z, Hoffman RM, Cheng XI, Liang L, Hu W, Yun S (2018) Effects of siRNA silencing of TUG1 and LCAL6 long non-coding RNAs on patient-derived xenograft of non-small cell lung cancer. Anticancer Res 38(1):179–186. https://doi.org/10.21873/anticanres.12206 PubMedCrossRef

25.

Jiang L, Wang W, Li G, Sun C, Ren Z, Sheng H, Gao H, Wang C, Yu H (2016) High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma. Cancer Chemother Pharmacol 78(2):333–339. https://doi.org/10.1007/s00280-016-3066-y CrossRefPubMed

26.

Kuang D, Zhang X, Hua S, Dong W, Li Z (2016) Long non-coding RNA TUG1 regulates ovarian cancer proliferation and metastasis via affecting epithelial-mesenchymal transition. Exp Mol Pathol 101(2):267–273. https://doi.org/10.1016/j.yexmp.2016.09.008 CrossRefPubMed

27.

Zhu J, Shi H, Liu H, Wang X, Li F (2017) Long non-coding RNA TUG1 promotes cervical cancer progression by regulating the miR-138-5p-SIRT1 axis. Oncotarget 8(39):65253–65264. https://doi.org/10.18632/oncotarget.18224 PubMedPubMedCentralCrossRef

28.

Warner SL, Bearss DJ, Han H, Von Hoff DD (2003) Targeting Aurora-2 kinase in cancer. Mol Cancer Ther 2(6):589–595PubMed

29.

Lee EC, Frolov A, Li R, Ayala G, Greenberg NM (2006) Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res 66(10):4996–5002. https://doi.org/10.1158/0008-5472.CAN-05-2796 CrossRefPubMed

30.

Lens SM, Voest EE, Medema RH (2010) Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 10(12):825–841. https://doi.org/10.1038/nrc2964 CrossRefPubMed

31.

Chuang TP, Wang JY, Jao SW, Wu CC, Chen JH, Hsiao KH, Lin CY, Chen SH, Su SY, Chen YJ, Chen YT, Wu DC, Li LH (2016) Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression. Oncotarget 7(29):45803–45818. https://doi.org/10.18632/oncotarget.9960 CrossRefPubMedPubMedCentral

32.

Eterno V, Zambelli A, Villani L, Tuscano A, Manera S, Spitaleri A, Pavesi L, Amato A (2016) AurkA controls self-renewal of breast cancer-initiating cells promoting wnt3a stabilization through suppression of miR-128. Sci Rep 6:28436. https://doi.org/10.1038/srep28436 CrossRefPubMedPubMedCentral

33.

Wu J, Yang L, Shan Y, Cai C, Wang S, Zhang H (2016) AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway. Oncol Lett 11(3):1889–1894. https://doi.org/10.3892/ol.2016.4110 CrossRefPubMedPubMedCentral

34.

Lucena-Araujo AR, de Oliveira FM, Leite-Cueva SD, dos Santos GA, Falcao RP, Rego EM (2011) High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia. Leuk Res 35(2):260–264. https://doi.org/10.1016/j.leukres.2010.07.034 CrossRefPubMed

35.

Ye D, Garcia-Manero G, Kantarjian HM, Xiao L, Vadhan-Raj S, Fernandez MH, Nguyen MH, Medeiros LJ, Bueso-Ramos CE (2009) Analysis of Aurora kinase A expression in CD34(+) blast cells isolated from patients with myelodysplastic syndromes and acute myeloid leukemia. J Hematop 2(1):2–8. https://doi.org/10.1007/s12308-008-0019-3 CrossRefPubMed

36.

Huang XF, Luo SK, Xu J, Li J, Xu DR, Wang LH, Yan M, Wang XR, Wan XB, Zheng FM, Zeng YX, Liu Q (2008) Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia. Blood 111(5):2854–2865. https://doi.org/10.1182/blood-2007-07-099325 CrossRefPubMed

Title: 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
Authors: Xinfeng Wang
Lina Zhang
Fan Zhao
Ruirong Xu
Jie Jiang
Chenglu Zhang
Hong Liu
Hongming Huang
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 8/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3315-8

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