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Grant support

Cancer Research UK and Friends of Kennington Cancer Research Fund (EF, ALH, JL), The Wellcome Trust (CB1, CC, IR), Royal College of Surgeons & British Urology Foundation (CB2, RMcC), European Union, ACGT (FB), Rhodes Scholarship (HG), Nuffield Medical Fellowship (AR), FIRC Studentship (EF). Biobanking supported by NIHR Biomedical Research Centre Oxford; Elsa Pardee Foundation (MI), American Cancer Society (MC, MI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Article

MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU

Publicated to:PLoS ONE. 5 (4): e10345- - 2010-09-14 5(4), DOI: 10.1371/journal.pone.0010345

Authors: Favaro, Elena; Ramachandran, Anassuya; McCormick, Robert; Gee, Harriet; Blancher, Christine; Crosby, Meredith; Devlin, Cecilia; Blick, Christopher; Buffa, Francesca; Li, Ji-Liang; Vojnovic, Borivoj; das Neves, Ricardo Pires; Glazer, Peter; Iborra, Francisco; Ivan, Mircea; Ragoussis, Jiannis; Harris, Adrian L.;

Affiliations

Indiana Univ, Indianapolis, IN 46204 USA - Author
Univ Oxford, Genom Grp, Wellcome Trust Ctr Human Genet, Oxford, England - Author
Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford, England - Author
Univ Oxford, John Radcliffe Hosp, Mol Oncol Labs, Weatherall Inst Mol Med, Oxford OX3 9DU, England - Author
Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA - Author
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Abstract

Background: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. Methods and Findings: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. Conclusions: Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.

Keywords
BiogenesisBreast-cancerDehydrogenaseGene-expressionHeadHelicasesInducible factorMutationRespirationSignature

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal PLoS ONE due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2010, it was in position 12/86, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 26.3, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-15, the following number of citations:

  • WoS: 251
  • Scopus: 289
  • OpenCitations: 280
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-15:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 165.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 165 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.25.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: India; United Kingdom; United States of America.