ArticleMolecular and cellular biology2012
Growth inhibition by miR-519 via multiple p21-inducing pathways.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
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- Conjunctival MicroRNA Expression Signature in Primary Sjögren's Syndrome Dry Eye: A NanoString-Based Bioinformatic Analysis.Investigative ophthalmology & visual science · 2025Article
- Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.Toxicology research · 2024Review
- MicroRNAs targeted mTOR as therapeutic agents to improve radiotherapy outcome.Cancer cell international · 2024Review
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- MicroRNAs miR-16 and miR-519 control meningioma cell proliferationFrontiers in oncology · 2023Article
- The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease.International journal of molecular sciences · 2022Review
- Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair.International journal of molecular sciences · 2022Review
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- Identification of MicroRNAs That Stabilize p53 in Human Papillomavirus-Positive Cancer Cells.Journal of virology · 2022Article
- Ion Channels and Transporters in Autophagy.Autophagy · 2022Article
- Non-coding RNAs: The link between maternal malnutrition and offspring metabolism.Frontiers in nutrition · 2022Review
- Identification of energy metabolism-related biomarkers for risk prediction of heart failure patients using random forest algorithm.Frontiers in cardiovascular medicine · 2022Article
- IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19.Journal of asthma and allergy · 2022Article
- The Landscape of Featured Metabolism-Related Genes and Imbalanced Immune Cell Subsets in Sepsis.Frontiers in genetics · 2022Article
- Review
- Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer.International journal of molecular sciences · 2020Review
- miR-519 regulates the proliferation of breast cancer cells via targeting human antigen R.Oncology letters · 2020Article
- HOTAIR inhibits the proliferation of glioblastoma cells by targeting miR-219.Cancer biomarkers : section A of Disease markers · 2020Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The microRNA miR-519 robustly inhibits cell proliferation, in turn triggering senescence and decreasing tumor growth. However, the molecular mediators of miR-519-elicited growth inhibition are unknown. Here, we systematically investigated the influence of miR-519 on gene expression profiles leading to growth cessation in HeLa human cervical carcinoma cells. By analyzing miR-519-triggered changes in protein and mRNA expression patterns and by identifying mRNAs associated with biotinylated miR-519, we uncovered two prominent subsets of miR-519-regulated mRNAs. One subset of miR-519 target mRNAs encoded DNA maintenance proteins (including DUT1, EXO1, RPA2, and POLE4); miR-519 repressed their expression and increased DNA damage, in turn raising the levels of the cyclin-dependent kinase (cdk) inhibitor p21. The other subset of miR-519 target mRNAs encoded proteins that control intracellular calcium levels (notably, ATP2C1 and ORAI1); their downregulation by miR-519 aberrantly elevated levels of cytosolic [Ca(2+)] storage in HeLa cells, similarly increasing p21 levels in a manner dependent on the Ca(2+)-activated kinases CaMKII and GSK3β. The rises in levels of DNA damage, the Ca(2+) concentration, and p21 levels stimulated an autophagic phenotype in HeLa and other human carcinoma cell lines. As a consequence, ATP levels increased, and the level of activity of the AMP-activated protein kinase (AMPK) declined, further contributing to the elevation in the abundance of p21. Our results indicate that miR-519 promotes DNA damage, alters Ca(2+) homeostasis, and enhances energy production; together, these processes elevate the expression level of p21, promoting growth inhibition and cell survival.
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Registered trials
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