ArticleCancer research2011
Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Pooled it
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Human miRNAs in Cancer: Statistical Trends and Cross Kingdom Approach.International journal of molecular sciences · 2025Article
- Mechanism by which CAP regulates the "cold-heat" balance in osteosarcoma model mice: an integrative study of metabolomics, transcriptomics, and network pharmacology.Journal of translational medicine · 2025Article
- Review
- Protrusion force and cell-cell adhesion-induced polarity alignment govern collective migration modes.Biophysical journal · 2025Article
- Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions.Cell death discovery · 2025Article
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- Investigating Expression Dynamics of miR-21 and miR-10b in Glioblastoma Cells In Vitro: Insights into Responses to Hypoxia and Secretion Mechanisms.International journal of molecular sciences · 2024Article
- An overview of challenges associated with exosomal miRNA isolation toward liquid biopsy-based ovarian cancer detection.Heliyon · 2024Review
- AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis.Cancers · 2023Article
- Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation.International immunopharmacology · 2022Review
- Article
- AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation.The FEBS journal · 2022Article
- Mammalian AKT, the Emerging Roles on Mitochondrial Function in Diseases.Aging and disease · 2022Review
- Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications.Molecular cancer · 2022Review
- Potential epigenetic molecular regulatory networks in ocular neovascularization.Frontiers in genetics · 2022Review
- OncomiRs as noncoding RNAs having functions in cancer: Their role in immune suppression and clinical implications.Frontiers in immunology · 2022Review
- Epigenetic Regulation During Hypoxia and Its Implications in Cancer.Sub-cellular biochemistry · 2022Article
- Small molecules with huge impacts: the role of miRNA-regulated PI3K pathway in human malignancies.Molecular biology reports · 2021Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The growth and survival of tumor cells in an unfavorable hypoxic environment depend upon their adaptability. Here, we show that both normal and tumor cells expressing the protein kinase Akt2 are more resistant to hypoxia than cells expressing Akt1 or Akt3. This is due to the differential regulation of microRNA (miR) 21, which is upregulated by hypoxia only in Akt2-expressing cells. By upregulating miR-21 upon oxygen deprivation, Akt2 downregulates PTEN and activates all three Akt isoforms. miR-21 also targets PDCD4 and Sprouty 1 (Spry1), and the combined downregulation of these proteins with PTEN is sufficient to confer resistance to hypoxia. Furthermore, the miR-21 induction by Akt2 during hypoxia depends upon the binding of NF-κB, cAMP responsive element-binding protein (CREB), and CBP/p300 to the miR-21 promoter, in addition to the regional acetylation of histone H3K9, all of which are under the control of Akt2. Analysis of the Akt2/miR-21 pathway in hypoxic MMTV-PyMT-induced mouse mammary adenocarcinomas and human ovarian carcinomas confirmed the activity of the pathway in vivo. Taken together, this study identifies a novel Akt2-dependent pathway that is activated by hypoxia and promotes tumor resistance via induction of miR-21.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.