RPL27A is a target of miR-595 and may contribute to the myelodysplastic phenotype through ribosomal dysgenesis

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
287 Downloads (Pure)

Abstract

We investigated the functional consequences following deletion of a microRNA (miR) termed miR-595 which resides on chromosome 7q and is localised within one of the commonly deleted regions identified for Myelodysplasia (MDS) with monosomy 7 (-7)/isolated loss of 7q (7q-). We identified several targets for miR-595, including a large ribosomal subunit protein RPL27A. RPL27A downregulation induced p53 activation, apoptosis and inhibited proliferation. Moreover, p53-independent effects were additionally identified secondary to a reduction in the ribosome subunit 60s. We confirmed that RPL27A plays a pivotal role in the maintenance of nucleolar integrity and ribosomal synthesis/maturation. Of note, RPL27A overexpression, despite showing no significant effects on p53 mRNA levels, did in fact enhance cellular proliferation. In normal CD34+ cells, RPL27A knockdown preferentially blocked erythroid proliferation and differentiation. Lastly, we show that miR-595 expression appears significantly downregulated in the majority of primary samples derived from MDS patients with (-7)/(7q-), in association with RPL27A upregulation. This significant downregulation of miR-595 is also apparent when higher risk MDS cases are compared to lower risk cases. The potential clinical importance of these findings requires further validation.
Original languageEnglish
Pages (from-to)47875-47890
Number of pages16
JournalOncotarget
Volume7
Issue number30
DOIs
Publication statusPublished - 25 Jun 2016

Keywords

  • Chromosome
  • Haemopoiesis
  • MicroRNA
  • Myelodysplasia
  • Ribosome

Fingerprint

Dive into the research topics of 'RPL27A is a target of miR-595 and may contribute to the myelodysplastic phenotype through ribosomal dysgenesis'. Together they form a unique fingerprint.

Cite this