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Genetics and Genomics

Synthetic miR-34a against solid tumours: a predictable failure

British Journal of Cancer volume 128, pages 478–480 (2023)Cite this article

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Summary

A prolific scientific literature attributes pro- or anti-oncogenic properties to many human microRNAs (“miRNAs”). While many of these studies are based on unpersuasive analyses, one candidate suppressor tumour miRNA, miR-34a, appeared convincing enough to be administered to human patients in a clinical trial—with disappointing outcomes. Here, we review possible reasons for that failure, and their implications for other miRNAs.

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References

  1. Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020;122:1630–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife. 2015;4:e05005.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pinzón N, Li B, Martinez L, Sergeeva A, Presumey J, Apparailly F, et al. microRNA target prediction programs predict many false positives. Genome Res. 2017;27:234–45.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mockly S, Seitz H. Inconsistencies and limitations of current microRNA target identification methods. Methods Mol Biol. 2019;1970:291–314.

    Article  CAS  PubMed  Google Scholar 

  7. Beg MS, Brenner AJ, Sachdev J, Borad M, Kang YK, Stoudemire J, et al. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest N. Drugs. 2017;35:180–8.

    Article  CAS  Google Scholar 

  8. Mockly S, Houbron E, Seitz H. A rationalized definition of general tumor suppressor microRNAs excludes miR-34a. Nucleic Acids Res. 2022;50:4703–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Concepcion CP, Han YC, Mu P, Bonetti C, Yao E, D’Andrea A, et al. Intact p53-dependent responses in miR-34-deficient mice. PLoS Genet. 2012;8:e1002797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kelnar K, Peltier HJ, Leatherbury N, Stoudemire J, Bader AG. Quantification of therapeutic miRNA mimics in whole blood from nonhuman primates. Anal Chem. 2014;86:1534–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kelnar K, Bader AG. A qRT-PCR method for determining the biodistribution profile of a miR-34a mimic. Methods Mol Biol. 2015;1317:125–33.

    Article  PubMed  Google Scholar 

  12. Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47:D155–62.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by Cancéropôle GSO “Émergence” grant, Projet Fondation ARC #PJA 20191209613 and a PhD fellowship from Fondation ARC (#ARCDOC4201912000100). The authors thank I. Busseau for critical reading of the manuscript.

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  1. Sophie Mockly

    Present address: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada

Authors and Affiliations

  1. Institut de Génétique Humaine, UMR 9002 CNRS and university of Montpellier, Montpellier, France

    Sophie Mockly & Hervé Seitz

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  1. Sophie Mockly
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SM and HS wrote the manuscript.

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Correspondence to Hervé Seitz.

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Mockly, S., Seitz, H. Synthetic miR-34a against solid tumours: a predictable failure. Br J Cancer 128, 478–480 (2023). https://doi.org/10.1038/s41416-022-02123-8

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