A feedback regulatory loop between HIF‐1α and miR‐21 in response to hypoxia in cardiomyocytes
Open accessAbstract
Accumulating evidence suggests that hypoxia‐inducible factor 1α (HIF‐1α) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF‐1α and miR‐21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF‐1α and miR‐21 expression. HIF‐1α knockdown increased cell apoptosis and reduced miR‐21 expression. Furthermore, we found that HIF‐1α transcriptionally enhanced miR‐21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR‐21 inhibition increased cell apoptosis and reduced HIF‐1α expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF‐1α‐miR‐21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.
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Modulating miR-21 expression in in vivo and in vitro studies shows clear and important phenotype changes.
“Modulating its expression in in vivo and in vitro studies show clear and important phenotype changes.”
From miR-21: a non‐specific biomarker of all maladies (2021) · cites this paper as [18]
Section 3.6 reports that inhibiting miR-21 increased apoptosis in hypoxic cardiomyocyte cells, supporting an in vitro phenotype change. The experiments described use cultured cells; our copy does not support the claim that this study also demonstrated phenotype changes in vivo. No page number is available in the indexed passage. (LLM, conf=0.88)
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Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251 · cited 1× · see citing works
“In normoxic condition, HIF-1a is hydroxylated by PHD proteins, and subsequently degraded via the recruitment of an ubiquitin-protein ligase VHL [5].”
BackgroundA MicroRNA Signature of Hypoxia
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., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055 · see citing works
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Research works printed but not linked: 3
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miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target
Serocki, M., Bartoszewska, S., Janaszak-Jasiecka, A., Ochocka, R. J., Collawn, J. F., & Bartoszewski, R. (2018) · Angiogenesis · doi:10.1007/s10456-018-9600-2 · Cited by 288 · see citing works
miR-21: a non‐specific biomarker of all maladies
Jenike, A. E., & Halushka, M. K. (2021) · Biomarker Research · doi:10.1186/s40364-021-00272-1 · Cited by 248 · see citing works
Moszyńska, A., Jaśkiewicz, M., Serocki, M., Cabaj, A., Crossman, D. K., Bartoszewska, S., Gebert, M., Dąbrowski, M., Collawn, J. F., & Bartoszewski, R. (2022) · The FASEB Journal · doi:10.1096/fj.202101987r · Cited by 53 · see citing works
Regulation of the HIF switch in human endothelial and cancer cells
Slawski, J., Jaśkiewicz, M., Barton, A., Kozioł, S., Collawn, J. F., & Bartoszewski, R. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151386 · Cited by 26 · see citing works
HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works
“Numerous miRNAs are transcriptionally induced by HIF-1, including miR-210, miR-146a, miR-145, miR-382, miR-191, miR-363, miR-421, miR-204, miR-30a, miR-21, miR-687, miR-155, miR-429, and miR-19a [48,122 – 136].”
- Authors
- Liu, Y., Nie, H., Zhang, K., Ma, D., Yang, G., Zheng, Z., Liu, K., Yu, B., Zhai, C., & Yang, S.
- Affiliations
- Harbin Medical University (CN)
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine (CN)
- Jiaxing University (CN)
- Corresponding author
- Zhai, Changlin
- Yang, Shuang
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2014-06-28
- Volume
- 588
- Issue
- 17
- Pages
- 3137-3146
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2022551564
- Cited by
- 94
- References
- 2
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 17 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 1
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Key Laboratory of Myocardial Ischemia, Harbin Medical University, Chinese Ministry of Education (KF201012)
- Wu Jieping Medical Foundation (320.6700.1155)
- Heilongjiang Natural Science Foundation (D201206)
- 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
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- HIF-1α, miR-21, hypoxia, cardiomyocytes, feedback regulatory loop, apoptosis, CBP/p300, PTEN/AKT pathway, myocardial ischemia, transcriptional regulation
- MeSH terms
- Animals, Cell Line, Cobalt, Gene Expression Regulation, Humans, Phosphorylation, Promoter Regions, Genetic, Transcription, Genetic, Cell Hypoxia, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Gene Silencing, Feedback, Physiological, Myocytes, Cardiac, MicroRNAs, p300-CBP Transcription Factors, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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