ArticleExperimental cell research2010
MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts.
Article in Experimental cell research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- MicroRNA‑microbiome cross‑kingdom networks drive inflammatory bowel disease through dynamic regulatory ecosystems (Review).International journal of molecular medicine · 2026Review
- Differential Expressions of Immunoregulatory microRNAs in Breast Milk of Mothers of Preterm Versus Term Infants: A Preliminary Study.Medicina (Kaunas, Lithuania) · 2025Article
- Daily Profile of miRNAs in the Rat Colon and In Silico Analysis of Their Possible Relationship to Colorectal Cancer.Biomedicines · 2025Article
- Sex Inclusion in Transcriptome Studies of Daily Rhythms.Journal of biological rhythms · 2023Article
- miRNA effects on gut homeostasis: therapeutic implications for inflammatory bowel disease.Trends in immunology · 2022Review
- Post-transcriptional modulators and mediators of the circadian clock.Chronobiology international · 2021Review
- Review
- Association of Circulating miRNA Expression with Preeclampsia, Its Onset, and Severity.Diagnostics (Basel, Switzerland) · 2021Article
- Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression.PloS one · 2019Article
- Micromanaging the gut: unravelling the regulatory pathways that mediate the intestinal adaptive response.Annals of the Royal College of Surgeons of England · 2018Article
- Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs.International journal of molecular sciences · 2017Article
- Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse.Investigative ophthalmology & visual science · 2016Article
- Diurnal Variations of Human Circulating Cell-Free Micro-RNA.PloS one · 2016Article
- MiRNA Analysis by Quantitative PCR in Preterm Human Breast Milk Reveals Daily Fluctuations of hsa-miR-16-5p.PloS one · 2015Article
- Intestinal epithelial barrier disruption through altered mucosal microRNA expression in human immunodeficiency virus and simian immunodeficiency virus infections.Journal of virology · 2014Article
- Article
- Defining suitable reference genes for RT-qPCR analysis on intestinal epithelial cells.Molecular biotechnology · 2013Article
- Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock.PloS one · 2013Article
- The induction of microRNA-16 in colon cancer cells by protein arginine deiminase inhibition causes a p53-dependent cell cycle arrest.PloS one · 2013Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsThe intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation.
methodsDiurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting.
resultsmir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16.
conclusionsThis is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.
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