ArticleJournal of molecular medicine (Berlin, Germany)2018
Oxidative stress-induced miRNAs modulate AKT signaling and promote cellular senescence in uterine leiomyoma.
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- A Systematic Review of the Role of Senescent Cells in Uterine Leiomyomas: Deciphering Molecular Pathways and Exploring Therapeutic Prospects.Reproductive sciences (Thousand Oaks, Calif.) · 2026Pooled it
- Cytotoxic and molecular effects of S-allylcysteine on uterine leiomyoma primary culture cells.Molecular biology reports · 2026Article
- Article
- Molecular Characteristics of the Endometrium in Polycystic Ovary Syndrome with Insulin Resistance.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Senescence-circadian interplay stratifies patient prognosis and reveals immune remodeling heterogeneity in colorectal cancer.Frontiers in immunology · 2026Article
- Cellular senescence, neuroinflammation, and microRNAs: Possible interactions driving aging and neurodegeneration in the hippocampal neurogenic niche.Aging brain · 2025Review
- MiRNAs related in signaling pathways of women's reproductive diseases: an overview.Molecular biology reports · 2024Review
- Review
- Identification of oxidative stress-related biomarkers in uterine leiomyoma: a transcriptome-combined Mendelian randomization analysis.Frontiers in endocrinology · 2024Article
- Pathways of Hypoxia-Inducible Factor (HIF) in the Orchestration of Uterine Fibroids Development.Life (Basel, Switzerland) · 2023Review
- Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.Antioxidants (Basel, Switzerland) · 2023Review
- Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products.International journal of molecular sciences · 2023Review
- Cellular senescence: the good, the bad and the unknown.Nature reviews. Nephrology · 2022Review
- Myometrial oxidative stress drives MED12 mutations in leiomyoma.Cell & bioscience · 2022Article
- Uterine Fibroids: Hiding in Plain Sight.Physiology (Bethesda, Md.) · 2022Review
- MicroRNAs as potential indicators of the development and progression of uterine leiomyoma.PloS one · 2022Article
- Chloroquine Attenuates Asthma Development by Restoring Airway Smooth Muscle Cell PhenotypeFrontiers in pharmacology · 2022Article
- miR-335-5p Inhibits Progression of Uterine Leiomyoma by Targeting ARGLU1.Computational and mathematical methods in medicine · 2022Article
- Review
- Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function.Fertility and sterility · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Uterine leiomyomas (ULM) grow under high oxidative stress due to a hypoxic microenvironment and defects in redox metabolism. AKT is one major pathway activated by reactive oxygen species (ROS) that maintains ULM growth and survival. We previously reported that AKT inactivated by AKT inhibitors can significantly induce cellular senescence in ULM cells. Since some miRNAs are induced by AKT inhibitors in an ROS-dependent manner, we proposed that these miRNAs may modulate AKT function and cellular senescence in ULM. We therefore established ex vivo models of a three-dimensional ULM spheroid culture system to study the role of miRNAs in cellular senescence. Four miRNAs, miR-29b, miR-181a, miR-182, and miR-200c, were found to induce cellular senescence in primary ULM and myometrium spheroid cultures when stably overexpressed. miR-181a and miR-182 were found to repress AKT3 and CCND2, respectively. Correspondingly, RNAi of AKT3 or CCND2 also induced cellular senescence and G0/G1 arrest. Thus, miR-181a and miR-182 may drive cellular senescence in ULM by repressing AKT3 and CCND2 activity, respectively. We further demonstrated that senescent ULM cells can be effectively removed by BH3 mimetic ABT263, which provides a new therapeutic venue for the treatment of ULM. Our findings suggest that miRNAs are potent modulators in regulating the ROS-AKT-cell cycle axis in uterine leiomyoma. KEY MESSAGES: A subset of oxidative stress-induced miRNAs is involved in AKT signaling in uterine leiomyoma. Overexpression of miR-181a and miR-182 resulted in cellular senescence in leiomyoma through repression of AKT3 and CCND2, respectively. Silencing of AKT3 and CCND2 drives leiomyoma cell into senescence and cycle arrest. Application of our newly developed 3D leiomyoma spheroids can provide a quick and reliable ex vivo model for cytopathologic and functional analysis. BH3 mimetics can effectively reduce the viability of miRNA-mediated senescent cells in leiomyoma.
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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.