miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cell Death and Differentiation Année : 2010

miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity.

M.-P. Puisségur
  • Fonction : Auteur
T. Bertero
L. Pradelli
  • Fonction : Auteur
S. Fourre
  • Fonction : Auteur
J. E. Ricci
  • Fonction : Auteur
P. Gounon
  • Fonction : Auteur

Résumé

Following the identification of a set of hypoxia-regulated microRNAs (miRNAs), recent studies have highlighted the importance of miR-210 and of its transcriptional regulation by the transcription factor hypoxia-inducible factor-1 (HIF-1). We report here that miR-210 is overexpressed at late stages of non-small cell lung cancer. Expression of miR-210 in lung adenocarcinoma A549 cells caused an alteration of cell viability associated with induction of caspase-3/7 activity. miR-210 induced a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. The expression profiling of cells overexpressing miR-210 revealed a specific signature characterized by enrichment for transcripts related to 'cell death' and 'mitochondrial dysfunction', including several subunits of the electron transport chain (ETC) complexes I and II. The transcript coding for one of these ETC components, SDHD, subunit D of succinate dehydrogenase complex (SDH), was validated as a bona fide miR-210 target. Moreover, SDHD knockdown mimicked miR-210-mediated mitochondrial alterations. Finally, miR-210-dependent targeting of SDHD was able to activate HIF-1, in line with previous studies linking loss-of-function SDH mutations to HIF-1 activation. miR-210 can thus regulate mitochondrial function by targeting key ETC component genes with important consequences on cell metabolism, survival and modulation of HIF-1 activity. These observations help explain contradictory data regarding miR-210 expression and its putative function in solid tumors.Cell Death and Differentiation advance online publication, 1 October 2010; doi:10.1038/cdd.2010.119.

Dates et versions

hal-00546747 , version 1 (14-12-2010)

Identifiants

Citer

M.-P. Puisségur, N. M. Mazure, T. Bertero, L. Pradelli, S. Grosso, et al.. miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity.. Cell Death and Differentiation, 2010, epub ahead of print. ⟨10.1038/cdd.2010.119⟩. ⟨hal-00546747⟩
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