ArticleThe Journal of biological chemistry2016
miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program That Includes SOX9 and the Ubiquitin Ligase Pathway.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Bta-miR-30f promotes adipogenesis and unsaturated fatty acid accumulation by targetingiScience · 2026Article
- Circulating MicroRNAs as diagnostic indicators in tuberculous Meningitis-A case -control study in North Indian population.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Milk-Derived Extracellular Vesicles and microRNAs: Potential Modulators of Intestinal Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Daily Profile of miRNAs in the Rat Colon and In Silico Analysis of Their Possible Relationship to Colorectal Cancer.Biomedicines · 2025Article
- White Adipocyte Stem Cell Expansion Through Infant Formula Feeding: New Insights into Epigenetic Programming Explaining the Early Protein Hypothesis of Obesity.International journal of molecular sciences · 2025Review
- Altered miRNA expression in duodenal tissue of celiac patients and the impact of a gluten-free diet: a preliminary study.Molecular biology reports · 2025Article
- miR-329b-5p Affects Sheep Intestinal Epithelial Cells againstVeterinary sciences · 2024Article
- Interaction between Rumen Epithelial miRNAs-Microbiota-Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep.International journal of molecular sciences · 2023Article
- Perspective: Milk microRNAs as Important Players in Infant Physiology and Development.Advances in nutrition (Bethesda, Md.) · 2021Article
- MicroRNA-30a-5p promotes differentiation in neonatal mouse spermatogonial stem cells (SSCs).Reproductive biology and endocrinology : RB&E · 2021Article
- Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state.Stem cell research & therapy · 2021Article
- Review
- CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn's disease.Scientific reports · 2021Article
- Role of Human Milk Bioactives on Infants' Gut and Immune Health.Frontiers in immunology · 2021Review
- Evolutionary dynamics of microRNA target sites across vertebrate evolution.PLoS genetics · 2020Article
- Probiotics and MicroRNA: Their Roles in the Host-Microbe Interactions.Frontiers in microbiology · 2020Review
- Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes.Frontiers in immunology · 2020Article
- Determination of the Excitatory Effects of MicroRNA-30 in the Self-Renewal and Differentiation Process of Neonatal Mouse Spermatogonial Stem Cells.Galen medical journal · 2020Article
- Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment.Theranostics · 2020Article
- Network-Based Selection of Candidate Markers and Assays to Assess the Impact of Oral Immune Interventions on Gut Functions.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Proliferation and differentiation of intestinal epithelial cells (IECs) occur in part through precise regulation of key transcription factors, such as SOX9. MicroRNAs (miRNAs) have emerged as prominent fine-tuners of transcription factor expression and activity. We hypothesized that miRNAs, in part through the regulation of SOX9, may mediate IEC homeostasis. Bioinformatic analyses of the SOX9 3'-UTR revealed highly conserved target sites for nine different miRNAs. Of these, only the miR-30 family members were both robustly and variably expressed across functionally distinct cell types of the murine jejunal epithelium. Inhibition of miR-30 using complementary locked nucleic acids (LNA30bcd) in both human IECs and human colorectal adenocarcinoma-derived Caco-2 cells resulted in significant up-regulation of SOX9 mRNA but, interestingly, significant down-regulation of SOX9 protein. To gain mechanistic insight into this non-intuitive finding, we performed RNA sequencing on LNA30bcd-treated human IECs and found 2440 significantly increased genes and 2651 significantly decreased genes across three time points. The up-regulated genes are highly enriched for both predicted miR-30 targets, as well as genes in the ubiquitin-proteasome pathway. Chemical suppression of the proteasome rescued the effect of LNA30bcd on SOX9 protein levels, indicating that the regulation of SOX9 protein by miR-30 is largely indirect through the proteasome pathway. Inhibition of the miR-30 family led to significantly reduced IEC proliferation and a dramatic increase in markers of enterocyte differentiation. This in-depth analysis of a complex miRNA regulatory program in intestinal epithelial cell models provides novel evidence that the miR-30 family likely plays an important role in IEC homeostasis.
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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.