Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth

MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected...

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Authors: Aguirre-Ena, X. (Xabier)|||/items/2a000d9c-cb5c-4734-a32c-4fef79998c86, Jimenez-Velasco, A. (A.)|||/items/c56a1ba7-243e-4226-897d-6d969da1d058, San-José-Enériz, E. (Edurne)|||/items/1c6714b1-f536-4b57-a755-83eca42e9964, Garate-Iturriagagoitia, L. (Leire)|||/items/8cb76f28-d2ce-4a71-a8b9-3e3e37a120a3, Bandres, E. (Eva)|||/items/a8f1d140-44cc-4ffe-8a76-3e49c4b4f78c, Cordeu, L. (Lucía)|||/items/9360af5e-bc98-4917-b059-eb7e42e4bd2d, Aparicio, O. (Óscar)|||/items/6cb4bb8d-b30b-4cde-aaec-5b2c411fb059, Saez, B. (Borja)|||/items/990d392a-7b64-40a1-8910-150af15b0f87, Navarro, G. (Germán)|||/items/b189b5d7-41ed-4f9b-8697-0958ddf51ccb, Vilas, A. (Amaia)|||/items/cebdc859-3ba2-4e25-b0e4-6a230b97a14f, Perez-Roger, I. (Ignacio)|||/items/bae2f5e6-69e6-409a-8482-0b3da07cdbac, Garcia-Foncillas, J. (Jesús)|||/items/f9f291e8-e98b-4de1-ab28-9d44e04f8a09, Heiniger, A. (A.)|||/items/c1560a2f-8133-4602-856c-ef23edb0a384, Calasanz-Abinzano, M.J. (Maria Jose)|||/items/a1f10f5c-06ce-47eb-bfd8-91fb972d8086, Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e, Roman-Gomez, J. (José)|||/items/bca25c5c-f92e-4fe2-b9a3-4b722345de85, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1
Format: article
Publication Date:2008
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/17940
Online Access:https://hdl.handle.net/10171/17940
Access Level:Open access
Keyword:Materias Investigacion::Ciencias de la Salud::Oncología
Área de Terapia Celular
Description
Summary:MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34+ cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML.

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