Skip to main content

Advertisement

Log in

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

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Objective

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

Results

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.

Conclusions

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • 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 5:2131–2148

    Article  PubMed  PubMed Central  Google Scholar 

  • Bassan R, Hoelzer D (2011) Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 29:532–543

    Article  PubMed  Google Scholar 

  • 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–e19

    Article  Google Scholar 

  • 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 1863:449–463

    Article  CAS  PubMed  Google Scholar 

  • 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 20:94–104

    Article  CAS  PubMed  Google Scholar 

  • Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21

    Article  CAS  PubMed  Google Scholar 

  • Grivennikov SI (2013) IL-11: a prominent pro-tumorigenic member of IL-6 family. Cancer Cell 24:10–1016

    Article  PubMed Central  Google Scholar 

  • 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 23:1317–1324

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 30:1663–1669

    Article  PubMed  PubMed Central  Google Scholar 

  • Inaba H, Greaves M, Mullighan CG (2013) Acute lymphoblastic leukaemia. Lancet 381:10–1016

    Article  PubMed Central  Google Scholar 

  • 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 36:1605–1611

    CAS  PubMed  Google Scholar 

  • 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 35:1575–1584

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Lin J (2016) Long noncoding RNA ZEB1-AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1. Am J Transl Res 8:4095–4105

    PubMed  PubMed Central  Google Scholar 

  • 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 333:213–221

    Article  CAS  PubMed  Google Scholar 

  • 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 17:1431

    Article  PubMed Central  Google Scholar 

  • 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 6:34245–34257

    PubMed  PubMed Central  Google Scholar 

  • 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 29:4157–4169

    Article  CAS  PubMed  Google Scholar 

  • Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499

    Article  CAS  PubMed  Google Scholar 

  • O’Shea JJ, Plenge R (2012) JAKs and STATs in immunoregulation and immune-mediated disease. Immunity 36:542–550

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 126:2404

    Article  CAS  PubMed  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  CAS  PubMed  Google Scholar 

  • Pui C, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371:1030–1043

    Article  CAS  PubMed  Google Scholar 

  • 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 360:2730–2741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  • 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 6:42130–42149

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 39:1437–1442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 8:11871–11876

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qing Wang.

Ethics declarations

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 4824 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Du, X., Yang, M. et al. LncRNA ZEB1-AS1 contributes to STAT3 activation by associating with IL-11 in B-lymphoblastic leukemia. Biotechnol Lett 39, 1801–1810 (2017). https://doi.org/10.1007/s10529-017-2421-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-017-2421-3

Keywords

Navigation