ArticleMolecular cancer2014
microRNA regulation of mammalian target of rapamycin expression and activity controls estrogen receptor function and RAD001 sensitivity.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology.International journal of molecular sciences · 2025Review
- Loss of Hormone Receptor Expression after Exposure to Fluid Shear Stress in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Cell-type-specific translational control of spatial working memory by the cap-binding protein 4EHP.Molecular brain · 2023Article
- Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer's-induced retinal vasculopathy by limiting Clec7a/Galectin-3Acta neuropathologica communications · 2022Article
- Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.The Journal of clinical investigation · 2022Article
- The Coordination of mTOR Signaling and Non-Coding RNA in Regulating Epileptic Neuroinflammation.Frontiers in immunology · 2022Review
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- ZEB2 regulates endocrine therapy sensitivity and metastasis in luminal a breast cancer cells through a non-canonical mechanism.Breast cancer research and treatment · 2021Article
- Review
- Lifetime Impact of Cow's Milk on Overactivation of mTORC1: From Fetal to Childhood Overgrowth, Acne, Diabetes, Cancers, and Neurodegeneration.Biomolecules · 2021Review
- MiR155 modulates vascular calcification by regulating Akt-FOXO3a signalling and apoptosis in vascular smooth muscle cells.Journal of cellular and molecular medicine · 2021Article
- Systematic Analysis of Intestinal MicroRNAs Expression in HCC: Identification of Suitable Reference Genes in Fecal Samples.Frontiers in genetics · 2019Article
- Modulated Autophagy by MicroRNAs in Osteoarthritis Chondrocytes.BioMed research international · 2019Review
- Tunneling Nanotubes Mediated microRNA-155 Intercellular Transportation Promotes Bladder Cancer Cells' Invasive and Proliferative Capacity.International journal of nanomedicine · 2019Article
- MicroRNAs as Mediators of Resistance Mechanisms to Small-Molecule Tyrosine Kinase Inhibitors in Solid Tumours.Targeted oncology · 2018Review
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- Emerging Role of MicroRNAs in mTOR Signaling.Cellular and molecular life sciences : CMLS · 2017Review
- Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells.BMC cancer · 2016Article
- Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans.Journal of hepatology · 2016Article
- miR-155 induced transcriptome changes in the MCF-7 breast cancer cell line leads to enhanced mitogen activated protein kinase signaling.Genes & cancer · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe AKT/mammalian target of rapamycin (mTOR) signaling pathway is regulated by 17α-estradiol (E2) signaling and mediates E2-induced proliferation and progesterone receptor (PgR) expression in breast cancer. METHODS AND
resultsHere we use deep sequencing analysis of previously published data from The Cancer Genome Atlas to demonstrate that expression of a key component of mTOR signaling, rapamycin-insensitive companion of mTOR (Rictor), positively correlated with an estrogen receptor-α positive (ERα+) breast tumor signature. Through increased microRNA-155 (miR-155) expression in the ERα+ breast cancer cells we demonstrate repression of Rictor enhanced activation of mTOR complex 1 (mTORC1) signaling with both qPCR and western blot. miR-155-mediated mTOR signaling resulted in deregulated ERα signaling both in cultured cells in vitro and in xenografts in vivo in addition to repressed PgR expression and activity. Furthermore we observed that miR-155 enhanced mTORC1 signaling (observed through western blot for increased phosphorylation on mTOR S2448) and induced inhibition of mTORC2 signaling (evident through repressed Rictor and tuberous sclerosis 1 (TSC1) gene expression). mTORC1 induced deregulation of E2 signaling was confirmed using qPCR and the mTORC1-specific inhibitor RAD001. Co-treatment of MCF7 breast cancer cells stably overexpressing miR-155 with RAD001 and E2 restored E2-induced PgR gene expression. RAD001 treatment of SCID/CB17 mice inhibited E2-induced tumorigenesis of the MCF7 miR-155 overexpressing cell line. Finally we demonstrated a strong positive correlation between Rictor and PgR expression and a negative correlation with Raptor expression in Luminal B breast cancer samples, a breast cancer histological subtype known for having an altered ERα-signaling pathway.
conclusionsmiRNA mediated alterations in mTOR and ERα signaling establishes a new mechanism for altered estrogen responses independent of growth factor stimulation.
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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.