HuR regulates β-tubulin isotype expression in ovarian cancer

Giuseppina Raspaglio, Ilaria De Maria, Flavia Filippetti, Enrica Martinelli, Gian Franco Zannoni, Silvia Prislei, Gabriella Ferrandina, Shohreh Shahabi, Giovanni Scambia, Cristiano Ferlini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III β-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3′ flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival.

Original languageEnglish (US)
Pages (from-to)5891-5900
Number of pages10
JournalCancer Research
Volume70
Issue number14
DOIs
StatePublished - Jul 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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