LncRNA ZEB1-AS1 contributes to STAT3 activation by associating with IL-11 in B-lymphoblastic leukemia
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.
KeywordsAcute lympho-blastic leukemia, IL-11 Long non-coding RNA, STAT3 ZEB1-AS1
This work was supported by Departmental sources.
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.
All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments.
- 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
- 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
- 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
- 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
- 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
- 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