Oncotarget

Research Papers:

Deregulation of linc-PINT in acute lymphoblastic leukemia is implicated in abnormal proliferation of leukemic cells

Andoni Garitano-Trojaola, Edurne San José-Enériz, Teresa Ezponda, Juan Pablo Unfried, Arantxa Carrasco-León, Nerea Razquin, Marina Barriocanal, Amaia Vilas-Zornoza, Bruno Sangro, Victor Segura, Felipe Prósper, Puri Fortes, Xabier Agirre _

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Oncotarget. 2018; 9:12842-12852. https://doi.org/10.18632/oncotarget.24401

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Abstract

Andoni Garitano-Trojaola1, Edurne San José-Enériz1, Teresa Ezponda1, Juan Pablo Unfried2, Arantxa Carrasco-León1, Nerea Razquin2, Marina Barriocanal2, Amaia Vilas-Zornoza1, Bruno Sangro3, Victor Segura4, Felipe Prósper1,5,*, Puri Fortes2,* and Xabier Agirre1,*

1Laboratory of Myeloproliferative Syndromes, Oncology Area, Foundation for Applied Medical Research, IDISNA, CIBERONC, University of Navarra, Pamplona, Spain

2Department of Gene Therapy and Hepatology, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain

3Liver Unit, CIBEREHD, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain

4Bioinformatics Unit, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain

5Hematology Service and Area of Cell Therapy, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain

*These authors have contributed equally to this work

Correspondence to:

Xabier Agirre, email: xaguirre@unav.es

Puri Fortes, email: pfortes@unav.es

Felipe Prósper, email: fprosper@unav.es

Keywords: acute leukemia; lncRNA; linc-PINT; epigenetic; HMOX1

Received: February 07, 2017    Accepted: January 19, 2018    Published: February 05, 2018

ABSTRACT

Long Non-Coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. Several lncRNAs are involved in cell proliferation and are deregulated in several human tumors. Few lncRNAs have been described to play a role in Acute Lymphoblastic Leukemia (ALL). In this study, we carried out a genome wide lncRNA expression profiling in ALL samples and peripheral blood samples obtained from healthy donors. We detected 43 lncRNAs that were aberrantly expressed in ALL. Interestingly, among them, linc-PINT showed a significant downregulation in T and B-ALL. Re-expression of linc-PINT in ALL cells induced inhibition of leukemic cell growth that was associated with apoptosis induction and cell cycle arrest in G2/M phase. linc-PINT induced the transcription of HMOX1 which reduced the viability of ALL cells. Intriguingly, we observed that treatment with anti-tumoral epigenetic drugs like LBH-589 (Panobinostat) and Curcumin induced the expression of linc-PINT and HMOX1 in ALL. These results indicate that the downregulation of linc-PINT plays a relevant role in the pathogenesis of ALL, and linc-PINT re-expression may be one of the mechanisms exerted by epigenetic drugs to reduce cell proliferation in ALL.


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