ArticlePloS one2013
miR-221/222 compensates for Skp2-mediated p27 degradation and is a primary target of cell cycle regulation by prostacyclin and cAMP.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension.International journal of molecular sciences · 2022Review
- MiR-4463 inhibits the migration of human aortic smooth muscle cells by AMOT.Bioscience reports · 2018Article
- Prostacyclin and EMT Pathway Markers for Monitoring Response to Lung Cancer Chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- MicroRNA 221 expression in theca and granulosa cells: hormonal regulation and function.Journal of animal science · 2018Article
- Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma.Oncology letters · 2017Article
- Bone Marrow Microenvironment Niche Regulates miR-221/222 in Acute Lymphoblastic Leukemia.Molecular cancer research : MCR · 2016Article
- Prostacyclin reverses the cigarette smoke-induced decrease in pulmonary Frizzled 9 expression through miR-31.Scientific reports · 2016Article
- Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening.Scientific reports · 2015Article
- Overexpression of caudal type homeobox transcription factor 2 inhibits the growth of the MGC-803 human gastric cancer cell line in vivo.Molecular medicine reports · 2015Article
- Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.BioMed research international · 2015Review
- Expression profiling of microRNAs in hippocampus of rats following traumatic brain injury.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014Article
- A FAK-Cas-Rac-lamellipodin signaling module transduces extracellular matrix stiffness into mechanosensitive cell cycling.Science signaling · 2014Article
- MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis.Molecular vision · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
p27(kip1) (p27) is a cdk-inhibitory protein with an important role in the proliferation of many cell types. SCF(Skp2) is the best studied regulator of p27 levels, but Skp2-mediated p27 degradation is not essential in vivo or in vitro. The molecular pathway that compensates for loss of Skp2-mediated p27 degradation has remained elusive. Here, we combine vascular injury in the mouse with genome-wide profiling to search for regulators of p27 during cell cycling in vivo. This approach, confirmed by RT-qPCR and mechanistic analysis in primary cells, identified miR-221/222 as a compensatory regulator of p27. The expression of miR221/222 is sensitive to proteasome inhibition with MG132 suggesting a link between p27 regulation by miRs and the proteasome. We then examined the roles of miR-221/222 and Skp2 in cell cycle inhibition by prostacyclin (PGI(2)), a potent cell cycle inhibitor acting through p27. PGI(2) inhibited both Skp2 and miR221/222 expression, but epistasis, ectopic expression, and time course experiments showed that miR-221/222, rather than Skp2, was the primary target of PGI(2). PGI(2) activates Gs to increase cAMP, and increasing intracellular cAMP phenocopies the effect of PGI(2) on p27, miR-221/222, and mitogenesis. We conclude that miR-221/222 compensates for loss of Skp2-mediated p27 degradation during cell cycling, contributes to proteasome-dependent G1 phase regulation of p27, and accounts for the anti-mitogenic effect of cAMP during growth inhibition.
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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.