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Article Open Access

Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia

  • Authors:
    • Jianmin Guan
    • Ping Liu
    • Aixia Wang
    • Bo Wang
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Heze Medical College, Heze, Shandong 274000, P.R. China, Department of Hematology, Heze Municipal Hospital, Heze, Shandong 274000, P.R. China, Department of Pharmacy, Chinese Medicine Hospital of Mudan District, Heze, Shandong 274000, P.R. China, Department of Blood Transfusion, Heze Municipal Hospital, Heze, Shandong 274000, P.R. China
    Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1490-1500
    |
    Published online on: July 23, 2020
       https://doi.org/10.3892/ijmm.2020.4683
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Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by the clonal accumulation of immature myeloid cells. Zinc finger E‑box binding homeobox 2 (ZEB2)‑antisense RNA 1 (AS1) has been verified to participate in the progression of several types of cancer, including AML. However, the potential mechanisms of ZEB2‑AS1 in AML have not yet been fully elucidated. The present study aimed to elucidate the role and regulatory mechanisms of ZEB2‑AS1 in AML. The expression of ZEB2‑AS1, microRNA‑122‑5p (miRNA/miR‑122‑5p) and polo‑like kinase 1 (PLK1) was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in AML tissues or cells. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) assay and apoptosis assay, respectively. The protein levels were examined by western blot analysis. The targeted sequence between miR‑122‑5p and ZEB2‑AS1 or PLK1 was predicted using an online database and verified by dual‑luciferase reporter assay. A mouse tumor xenograft model was established to confirm the effects of ZEB2‑AS1 on tumor growth in vivo. The results revealed that the expression levels of ZEB2‑AS1 and PLK1 were upregulated, while those of miR‑122‑5p were downregulated in AML tissues and cells. The knockdown of ZEB2‑AS1 inhibited proliferation and induced apoptosis in vitro, and inhibited tumor growth in vivo. By experimental verification, ZEB2‑AS1 was found to negatively regulate miR‑122‑5p expression and PLK1 was found to be a target gene of miR‑122‑5p. Furthermore, ZEB2‑AS1 was verified to regulate the expression of PLK1 by sponging miR‑122‑5p in AML cells. On the whole, the findings of the present study demonstrate that ZEB2‑AS1 promotes cell proliferation and inhibits apoptosis, at least partly by targeting PLK1 mediated by miR‑122‑5p in AML cells.
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1 

Short NJ, Rytting ME and Cortes JE: Acute myeloid leukaemia. Lancet. 392:593–606. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Burnett A, Wetzler M and Löwenberg B: Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 29:487–494. 2011. View Article : Google Scholar : PubMed/NCBI

3 

De Kouchkovsky I and Abdul-Hay M: Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J. 6:e4412016. View Article : Google Scholar

4 

Roboz GJ: Current treatment of acute myeloid leukemia. Curr Opin Oncol. 24:711–719. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Bullinger L, Döhner K and Döhner H: Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 35:934–946. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Ernst C and Morton CC: Identification and function of long non-coding RNA. Front Cell Neurosci. 7:1682013. View Article : Google Scholar : PubMed/NCBI

7 

Li CH and Chen Y: Targeting long non-coding RNAs in cancers: Progress and prospects. Int J Biochem Cell Biol. 45:1895–1910. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Liu Y, Cheng Z, Pang Y, Cui L, Qian T, Quan L, Zhao H, Shi J, Ke X and Fu L: Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia. J Hematol Oncol. 12:512019. View Article : Google Scholar : PubMed/NCBI

9 

Xu C, Cui H, Li H, Wu Y, An H and Guo C: Long non-coding RNA ZEB2-AS1 expression is associated with disease progression and predicts outcome in gastric cancer patients. J BUON. 24:663–671. 2019.PubMed/NCBI

10 

Guo Y, Hu Y, Hu M, He J and Li B: Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis in human lung cancer cells. Oncol Lett. 15:5220–5226. 2018.PubMed/NCBI

11 

Gao H, Gong N, Ma Z, Miao X, Chen J, Cao Y and Zhang G: LncRNA ZEB2-AS1 promotes pancreatic cancer cell growth and invasion through regulating the miR-204/HMGB1 axis. Int J Biol Macromol. 116:545–551. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Shi X, Li J, Ma L, Wen L, Wang Q, Yao H, Ruan C, Wu D, Zhang X and Chen S: Overexpression of ZEB2-AS1 lncRNA is associated with poor clinical outcomes in acute myeloid leukemia. Oncol Lett. 17:4935–4947. 2019.PubMed/NCBI

13 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Kavitha N, Vijayarathna S, Jothy SL, Oon CE, Chen Y, Kanwar JR and Sasidharan S: MicroRNAs: Biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis. Asian Pac J Cancer Prev. 15:7489–7497. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Yang J, Yuan Y, Yang X, Hong Z and Yang L: Decreased expression of microRNA-122 is associated with an unfavorable prognosis in childhood acute myeloid leukemia and function analysis indicates a therapeutic potential. Pathol Res Pract. 213:1166–1172. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Zhang TJ, Qian Z, Wen XM, Zhou JD, Li XX, Xu ZJ, Ma JC, Zhang ZH, Lin J and Qian J: Lower expression of bone marrow miR-122 is an independent risk factor for overall survival in cytogenetically normal acute myeloid leukemia. Pathol Res Pract. 214:896–901. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Colicino EG and Hehnly H: Regulating a key mitotic regulator, polo-like kinase 1 (PLK1). Cytoskeleton (Hoboken). 75:481–494. 2018. View Article : Google Scholar

19 

Weng Ng WT, Shin JS, Roberts TL, Wang B and Lee CS: Molecular interactions of polo-like kinase 1 in human cancers. J Clin Pathol. 69:557–562. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Brandwein JM: Targeting polo-like kinase 1 in acute myeloid leukemia. Ther Adv Hematol. 6:80–87. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language. Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

23 

Khwaja A, Bjorkholm M, Gale RE, Levine RL, Jordan CT, Ehninger G, Bloomfield CD, Estey E, Burnett A, Cornelissen JJ, et al: Acute myeloid leukaemia. Nat Rev Dis Primers. 2:160102016. View Article : Google Scholar : PubMed/NCBI

24 

Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, et al: Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 361:1058–1066. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Young AL, Tong RS, Birmann BM and Druley TE: Clonal haematopoiesis and risk of acute myeloid leukemia. Haematologica. 104:2410–2417. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Rathinasamy B and Velmurugan BK: Role of lncRNAs in the cancer development and progression and their regulation by various phytochemicals. Biomed Pharmacother. 102:242–248. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Zhang G, Li H, Sun R, Li P, Yang Z, Liu Y, Wang Z, Yang Y and Yin C: Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2. J Cell Mol Med. 23:3271–3279. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Wu X, Yan T, Wang Z, Wu X, Cao G and Zhang C: LncRNA ZEB2-AS1 promotes bladder cancer cell proliferation and inhibits apoptosis by regulating miR-27b. Biomed Pharmacother. 96:299–304. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Duan Y, Dong Y, Dang R, Hu Z, Yang Y, Hu Y and Cheng J: MiR-122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells. Cell Biol Int. 42:1564–1574. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Liu YH, Liu JL, Wang Z, Zhu XH, Chen XB and Wang MQ: MiR-122-5p suppresses cell proliferation, migration and invasion by targeting SATB1 in nasopharyngeal carcinoma. Eur Rev Med Pharmacol Sci. 23:622–629. 2019.PubMed/NCBI

31 

Zhang L, Wang Y, Sun J, Ma H and Guo C: LINC00205 promotes proliferation, migration and invasion of HCC cells by targeting miR-122-5p. Pathol Res Pract. 215:1525152019. View Article : Google Scholar : PubMed/NCBI

32 

Xu Z, Liu G, Zhang M, Zhang Z, Jia Y, Peng L, Zhu Y, Hu J, Huang R and Sun X: MiR-122-5p inhibits the proliferation, invasion and growth of bile duct carcinoma cells by targeting ALDOA. Cell Physiol Biochem. 48:2596–2606. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Ann Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Liu Z, Sun Q and Wang X: PLK1, a potential target for cancer therapy. Transl Oncol. 10:22–32. 2017. View Article : Google Scholar

35 

Dang SC, Fan YY, Cui L, Chen JX, Qu JG and Gu M: PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models. Onco Targets Ther. 11:6239–6247. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Xu C, Li S, Chen T, Hu H, Ding C, Xu Z, Chen J, Liu Z, Lei Z, Zhang HT, et al: MiR-296-5p suppresses cell viability by directly targeting PLK1 in non-small cell lung cancer. Oncol Rep. 35:497–503. 2016. View Article : Google Scholar

37 

Li J, Wang R, Schweickert PG, Karki A, Yang Y, Kong Y, Ahmad N, Konieczny SF and Liu X: Plk1 inhibition enhances the efficacy of gemcitabine in human pancreatic cancer. Cell Cycle. 15:711–719. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Guan J, Liu P, Wang A and Wang B: Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia. Int J Mol Med 46: 1490-1500, 2020.
APA
Guan, J., Liu, P., Wang, A., & Wang, B. (2020). Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia. International Journal of Molecular Medicine, 46, 1490-1500. https://doi.org/10.3892/ijmm.2020.4683
MLA
Guan, J., Liu, P., Wang, A., Wang, B."Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia". International Journal of Molecular Medicine 46.4 (2020): 1490-1500.
Chicago
Guan, J., Liu, P., Wang, A., Wang, B."Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia". International Journal of Molecular Medicine 46, no. 4 (2020): 1490-1500. https://doi.org/10.3892/ijmm.2020.4683
Copy and paste a formatted citation
x
Spandidos Publications style
Guan J, Liu P, Wang A and Wang B: Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia. Int J Mol Med 46: 1490-1500, 2020.
APA
Guan, J., Liu, P., Wang, A., & Wang, B. (2020). Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia. International Journal of Molecular Medicine, 46, 1490-1500. https://doi.org/10.3892/ijmm.2020.4683
MLA
Guan, J., Liu, P., Wang, A., Wang, B."Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia". International Journal of Molecular Medicine 46.4 (2020): 1490-1500.
Chicago
Guan, J., Liu, P., Wang, A., Wang, B."Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia". International Journal of Molecular Medicine 46, no. 4 (2020): 1490-1500. https://doi.org/10.3892/ijmm.2020.4683
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