Biotechnology Letters

, Volume 39, Issue 12, pp 1801–1810 | Cite as

LncRNA ZEB1-AS1 contributes to STAT3 activation by associating with IL-11 in B-lymphoblastic leukemia

  • Qing Wang
  • Xiaoli Du
  • Min Yang
  • Shishan Xiao
  • Jun Cao
  • Jun Song
  • Linhui Wang
Original Research Paper



To investigate the role of lncRNA ZEB1-AS1 in B-lineage acute lymphoblastic leukemia (B-ALL).


ZEB1-AS1 levels were aberrantly up-regulated in B-ALL. All correlated with STAT3 activation and IL-11 production. Moreover, a high level of ZEB1-AS1 predicted poor prognosis of B-ALL patients. Mechanistically, ZEB1-AS1 could bind to IL-11 and promote IL-11 stability. Down-regulation of ZEB1-AS1 decreased IL-11 production of human bone marrow stromal cells (BMSCs), which led to suppressed proliferation and inhibited IL-11/STAT3 pathway in BALL-1 cells.


ZEB1-AS1 promotes the activation of IL-11/STAT3 signaling pathway by associating with IL-11 in B-ALL.


Acute lympho-blastic leukemia, IL-11 Long non-coding RNA, STAT3 ZEB1-AS1 



This work was supported by Departmental sources.

Supporting information

Supplementary Fig. 1—Expressions of ZEB1 and ZEB1-AS1.

Supplementary Fig. 2—Effects of ZEB1-AS1 knockdown in BALL-1 cells.

Supplementary Fig. 3—Effects of ZEB1-AS1 knockdown in HS-5 cells.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments.

Supplementary material

10529_2017_2421_MOESM1_ESM.doc (4.7 mb)
Supplementary material 1 (DOC 4824 kb)


  1. Aparicio-Siegmund S, Sommer J, Monhasery N, Schwanbeck R, Keil E, Finkenstädt D, Pfeffer K, Rose-John S, Scheller J, Garbers C (2014) Inhibition of protein kinase II (CK2) prevents induced signal transducer and activator of transcription (STAT) 1/3 and constitutive STAT3 activation. Oncotarget 5:2131–2148CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bassan R, Hoelzer D (2011) Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 29:532–543CrossRefPubMedGoogle Scholar
  3. Brazão TF, Johnson JS, Müller J, Heger A, Ponting CP, Tybulewicz VLJ (2015) Long noncoding RNAs in B-cell development and activation. Blood 128:e10–e19CrossRefGoogle Scholar
  4. Chiarini F, Lonetti A, Evangelisti C, Buontempo F, Orsini E, Evangelisti C, Cappellini A, Neri LM, McCubrey JA, Martelli AM (2016) Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: from biology to therapeutic targeting. Biochim Biophys Acta 1863:449–463CrossRefPubMedGoogle Scholar
  5. Elsafadi M, Manikandan M, Alajez NM, Hamam R, Dawud RA, Aldahmash A, Iqbal Z, Alfayez M, Kassem M, Mahmood A (2017) MicroRNA-4739 regulates osteogenic and adipocytic differentiation of immortalized human bone marrow stromal cells via targeting LRP3. Stem Cell Res 20:94–104CrossRefPubMedGoogle Scholar
  6. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21CrossRefPubMedGoogle Scholar
  7. Grivennikov SI (2013) IL-11: a prominent pro-tumorigenic member of IL-6 family. Cancer Cell 24:10–1016CrossRefPubMedCentralGoogle Scholar
  8. Hu Z, Zhang H, Tang L, Lou M, Geng Y (2017) Silencing nc886, a non-coding RNA, induces apoptosis of human endometrial cancer cells-1A in vitro. Med Sci Monit 23:1317–1324CrossRefPubMedPubMedCentralGoogle Scholar
  9. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL (2012) Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol 30:1663–1669CrossRefPubMedPubMedCentralGoogle Scholar
  10. Inaba H, Greaves M, Mullighan CG (2013) Acute lymphoblastic leukaemia. Lancet 381:10–1016CrossRefPubMedCentralGoogle Scholar
  11. Kotake Y, Kitagawa K, Ohhata T, Sakai S, Uchida C, Niida H, Naemura M, Kitagawa M (2016) Long non-coding RNA, PANDA, contributes to the stabilization of p53 tumor suppressor protein. Anticancer Res 36:1605–1611PubMedGoogle Scholar
  12. Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Deng X, Chen H, Shen B, Peng C, Li H, Zhan Q, Zhu Z (2016) Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene 35:1575–1584CrossRefPubMedGoogle Scholar
  13. Liu C, Lin J (2016) Long noncoding RNA ZEB1-AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1. Am J Transl Res 8:4095–4105PubMedPubMedCentralGoogle Scholar
  14. Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013) Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett 333:213–221CrossRefPubMedGoogle Scholar
  15. Lv Q, Hu L, Chen S, Sun B, Fu M, Qin C, Qu Q, Wang G, He C, Zhou H (2016) A long noncoding RNA ZEB1-AS1 promotes tumorigenesis and predicts poor prognosis in glioma. Int J Mol Sci 17:1431CrossRefPubMedCentralGoogle Scholar
  16. Montresor A, Toffali L, Mirenda M, Rigo A, Vinante F, Laudanna C (2015) JAK2 tyrosine kinase mediates integrin activation induced by CXCL12 in B-cell chronic lymphocytic leukemia. Oncotarget 6:34245–34257PubMedPubMedCentralGoogle Scholar
  17. Nakahata S, Yamazaki S, Nakauchi H, Morishita K (2010) Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to TGF-β1-mediated growth suppression in adult T-cell leukemia/lymphoma. Oncogene 29:4157–4169CrossRefPubMedGoogle Scholar
  18. Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499CrossRefPubMedGoogle Scholar
  19. O’Shea JJ, Plenge R (2012) JAKs and STATs in immunoregulation and immune-mediated disease. Immunity 36:542–550CrossRefPubMedPubMedCentralGoogle Scholar
  20. Polak R, de Rooij B, Pieters R, den Boer ML (2015) B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment. Blood 126:2404CrossRefPubMedGoogle Scholar
  21. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641CrossRefPubMedGoogle Scholar
  22. Pui C, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371:1030–1043CrossRefPubMedGoogle Scholar
  23. Pui C, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Raimondi SC, Onciu M, Coustan-Smith E, Kun LE, Jeha S, Cheng C, Howard SC, Simmons V, Bayles A, Metzger ML, Boyett JM, Leung W, Handgretinger R, Downing JR, Evans WE, Relling MV (2009) Treatment of childhood acute lymphoblastic leukemia without prophylactic cranial irradiation. N Engl J Med 360:2730–2741CrossRefPubMedPubMedCentralGoogle Scholar
  24. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29CrossRefPubMedGoogle Scholar
  25. Trimarco V, Ave E, Facco M, Chiodin G, Frezzato F, Martini V, Gattazzo C, Lessi F, Giorgi CA, Visentin A, Castelli M, Severin F, Zambello R, Piazza F, Semenzato G, Trentin L (2015) Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival. Oncotarget 6:42130–42149CrossRefPubMedPubMedCentralGoogle Scholar
  26. Uy GL, Hsu YS, Schmidt AP, Stock W, Fletcher TR, Trinkaus KM, Westervelt P, DiPersio JF, Link DC (2015) Targeting bone marrow lymphoid niches in acute lymphoblastic leukemia. Leuk Res 39:1437–1442CrossRefPubMedPubMedCentralGoogle Scholar
  27. Wang Y, Bai Y, Yao W, Guo L, Wang Z (2015) Expression of long non-coding RNA ZEB1-AS1 in esophageal squamous cell carcinoma and its correlation with tumor progression and patient survival. Int J Clin Exp Pathol 8:11871–11876PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Qing Wang
    • 1
  • Xiaoli Du
    • 1
  • Min Yang
    • 1
  • Shishan Xiao
    • 1
  • Jun Cao
    • 1
  • Jun Song
    • 1
  • Linhui Wang
    • 1
  1. 1.Department of HematologyGuizhou Provincial People’s HospitalGuiyangChina

Personalised recommendations