A MicroRNA Signature of Hypoxia
Open accessAbstract
Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.
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miR-23a was induced under hypoxic circumstances and can act upon pro-apoptotic signals to promote tumor formation and oncogenic transformation.
“miR-23a was induced under hypoxic circumstances and can ultimately act upon pro-apoptotic signals to promote tumor formation and oncogenic transformation [89].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [89]
The Results table reports increased miR-23a expression under hypoxia. The Discussion predicts that miR-23 targets pro-apoptotic components, but the paper does not demonstrate this effect for miR-23a or show that it promotes tumor formation or oncogenic transformation. The Results report caspase inhibition for miR-26, miR-107, and miR-210 instead. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHypoxia, a general feature of all solid tumors, can induce miR-21 expression.
“Another factor that can induce miR-21 expression is hypoxia, a general feature of all solid tumors (30).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [30]
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- Authors
- Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., Calin, G. A., & Ivan, M.
- Affiliations
- Tufts Medical Center (US)
- University of Ferrara (IT)
- The Ohio State University (US)
- Comprehensive Cancer Center, Ohio State University
- Corresponding author
- Ivan, Mircea
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-03-01
- Volume
- 27
- Issue
- 5
- Pages
- 1859-1867
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1820461
- OpenAlex
- W2116000203
- Cited by
- 1,055
- References
- 31
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 26 · 2023: 32 · 2022: 45 · 2021: 50 · 2020: 43 · 2019: 54 · 2018: 38 · 2017: 70 · 2016: 63 · 2015: 73 · 2014: 91 · 2013: 93 · 2012: 81
- FWCI
- 16.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-34928, P30DK034928)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- microRNA, hypoxia, hypoxia-inducible factor, miR-210, miR-26, miR-107, tumor microenvironment, tumor formation, apoptosis, miRNA expression profiling, non-coding RNA regulation
- MeSH terms
- Breast Neoplasms, Colonic Neoplasms, Female, Humans, Luciferases, Plasmids, Transfection, Cell Hypoxia, Apoptosis, Genes, Reporter, HT29 Cells, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, HCT116 Cells, Cell Line, Tumor, Chromatin Immunoprecipitation
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