MicroRNA and proliferation control in chronic lymphocytic leukemia: Functional relationship between miR-221/222 cluster and p27

Michela Frenquelli, Marta Muzio, Cristina Scielzo, Claudia Fazi, Lydia Scarfò, Claudia Rossi, Giuliana Ferrari, Paolo Ghia, Federico Caligaris-Cappio

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated functional relationships between microRNA 221/222 (miR-221/222) cluster and p27, a key regulator of cell cycle, in chronic lymphocytic leukemia (CLL). The enforced expression of miR-221/222 in the CLL cell line MEC1 induced a significant down-regulation of p27 protein and conferred a proliferative advantage to the transduced cells that exhibited faster progression into the S phase of the cell cycle. Accordingly, expression of miR-221/miR-222 and p27 was found to be inversely related in leukemic cells obtained from peripheral blood (PB) of 38 patients with CLL. Interestingly, when miR-221/222 and p27 protein were evaluated in different anatomic compartments (lymph nodes or bone marrow) of the same patients, increased expression of the 2 miRNAs became apparent compared with PB. This finding was paralleled by a low expression of p27. In addition, when CLL cells were induced in vitro to enter cell cycle (eg, with cytosine phosphate guanine oligodeoxynucleotide), a significant increase of miR-221/222 expression and a marked down-regulation of p27 protein were evident. These data indicate that the miR-221/222 cluster modulates the expression of p27 protein in CLL cells and lead to suggest that miR-221/222 and p27 may represent a regulatory loop that helps maintaining CLL cells in a resting condition.

Original languageEnglish
Pages (from-to)3949-3959
Number of pages11
JournalBlood
Volume115
Issue number19
DOIs
Publication statusPublished - May 13 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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