ArticleMolecular and cellular biology2016
A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- The Role of microRNAs in Gene Expression and Signaling Response of Tumor Cells to an Acidic Environment.International journal of molecular sciences · 2023Article
- Exosome Secretion and Epithelial-Mesenchymal Transition in Ovarian Cancer Are Regulated by Phospholipase D.International journal of molecular sciences · 2022Article
- D-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models.Molecular and cellular biochemistry · 2020Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Somatic Mutations in miRNA Genes in Lung Cancer-Potential Functional Consequences of Non-Coding Sequence Variants.Cancers · 2019Article
- How miRs and mRNA deadenylases could post-transcriptionally regulate expression of tumor-promoting protein PLD.Advances in biological regulation · 2018Review
- Phospholipase D and Its Essential Role in Cancer.Molecules and cells · 2017Review
- MiR-887 Promotes the Progression of Hepatocellular Carcinoma via Targeting VHL.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and nutrient starvation for 3 to 6 h increase expression even further. However, after prolonged (>12-h) starvation, PLD levels return to basal or lower levels. The mechanism for this is as follows. First, during initial starvation, an elevated PA (the product of PLD enzymatic activity) activates mTOR and S6K, known to inhibit apoptosis, and enhances cell migration especially in post-epithelial-to-mesenchymal transition (post-EMT) cancer cells. Second, continued PA production in later starvation induces expression of PLD-targeting microRNA 203 (miR-203), miR-887, miR-3619-5p, and miR-182, which reduce PLD translation. We provide direct evidence for a feedback loop, whereby PLD induction upon starvation leads to PA, which induces expression of miRNAs, which in turn inhibits PLD2 translation. The physiological relevance for breast cancer cells is that as PA can activate cell invasion, then, due to the negative feedback, it can deprive mTOR and S6K of their natural activator. It can further prevent inhibition of apoptosis and allow cells to survive nutrient deprivation, which normal cells cannot do.
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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.