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MicroRNA-222 Promotes the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Targeting P27 and TIMP3
- Source :
- Cellular Physiology and Biochemistry, Vol 43, Iss 1, Pp 282-292 (2017)
- Publication Year :
- 2017
- Publisher :
- Cell Physiol Biochem Press GmbH & Co KG, 2017.
-
Abstract
- Background/Aims: Aberrant vascular smooth muscle cell (VSMC) proliferation plays an important role in the development of pulmonary artery hypertension (PAH). Dysregulated microRNAs (miRNAs, miRs) have been implicated in the progression of PAH. miR-222 has a pro-proliferation effect on VSMCs while it has an anti-proliferation effect on vascular endothelial cells (ECs). As the biological function of a single miRNA could be cell-type specific, the role of miR-222 in pulmonary artery smooth muscle cell (PASMC) proliferation is not clear and deserves to be explored. Methods: PASMCs were transfected with miR-222 mimic or inhibitor and PASMC proliferation was determined by Western blot for PCNA, Ki-67 and EdU staining, and cell number counting. The target genes of miR-222 including P27 and TIMP3 were determined by luciferase assay and Western blot. In addition, the functional rescue experiments were performed based on miR-222 inhibitor and siRNAs to target genes. Results: miR-222 mimic promoted PASMC proliferation while miR-222 inhibitor decreased that. TIMP3 was identified to be a direct target gene of miR-222 based on luciferase assay. Meanwhile, P27 and TIMP3 were up-regulated by miR-222 inhibitor and down-regulated by miR-222 mimic. Moreover, P27 siRNA and TIMP3 siRNA could both attenuate the anti-proliferation effect of miR-222 inhibitor in PASMCs, supporting that P27 and TIMP3 are at least partially responsible for the regulatory effect of miR-222 in PASMCs. Conclusion: miR-222 promotes PASMC proliferation at least partially through targeting P27 and TIMP3.
- Subjects :
- 0301 basic medicine
Male
Small interfering RNA
Vascular smooth muscle
Physiology
Cell
Proliferation
Muscle, Smooth, Vascular
lcsh:Physiology
Rats, Sprague-Dawley
lcsh:QD415-436
RNA, Small Interfering
Pulmonary artery hypertension
Cells, Cultured
biology
medicine.diagnostic_test
lcsh:QP1-981
Chemistry
Transfection
Cell Hypoxia
Up-Regulation
medicine.anatomical_structure
Pulmonary artery smooth muscle cells
Cardiology
RNA Interference
Cyclin-Dependent Kinase Inhibitor p27
medicine.medical_specialty
MiR-222
Down-Regulation
Pulmonary Artery
lcsh:Biochemistry
03 medical and health sciences
Western blot
Internal medicine
Proliferating Cell Nuclear Antigen
microRNA
medicine
Animals
Luciferase
Cell Proliferation
Tissue Inhibitor of Metalloproteinase-3
Antagomirs
Proliferating cell nuclear antigen
Rats
MicroRNAs
030104 developmental biology
Ki-67 Antigen
Microscopy, Fluorescence
biology.protein
Cancer research
Subjects
Details
- Language :
- English
- ISSN :
- 14219778 and 10158987
- Volume :
- 43
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cellular Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....19359220c2d4ee3488d9d79fe0a8226a