Overexpressed Hsa_circ_0001326 Contributes to the Decreased Cell Viability in SWAN71 Cells by Regulating MiR-186-5p/p27 Kip1 Axis
Autor: | Zhaoxia Zhong, Wen Xu, Juan Tan, Naiyi Zhang |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Pharmaceutical Science Cell Line Cell Physiological Phenomena Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin Cyclin E medicine Humans Propidium iodide Viability assay Oncogene Proteins Pharmacology medicine.diagnostic_test Chemistry Cell growth Cyclin-Dependent Kinase 2 RNA Circular General Medicine Cell cycle Molecular biology Up-Regulation MicroRNAs 030104 developmental biology Apoptosis Gene Knockdown Techniques 030220 oncology & carcinogenesis G1 phase Cyclin-Dependent Kinase Inhibitor p27 |
Zdroj: | Biological and Pharmaceutical Bulletin. 44:507-514 |
ISSN: | 1347-5215 0918-6158 |
DOI: | 10.1248/bpb.b20-00755 |
Popis: | Preeclampsia (PE) is a severe pregnancy-specific complication responsible for a majority of maternal and fetal mortality. The dysfunction of trophoblast cells is known to be associated with the etiology of PE. Moreover, elevated expression of hsa_circ_0001326 was found in patients with PE without elucidating specific mechanisms. Thus, this study aimed to investigate the role of hsa_circ_0001326 in the dysfunction of trophoblast cells in vitro. Human trophoblast SWAN71 cells were used in this study. Cell proliferation, apoptosis and cell cycle were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, cell counting kit-8 assay, Annexin V/propidium iodide (PI) staining and flow cytometry, respectively. Dual luciferase assay was performed to validate the predicted targets. Additionally, Western blot was conducted for protein detection. The results indicated overexpression (OE) of hsa_circ_0001326 remarkably decreased the viability and proliferation of SWAN71 cells. MiR-186-5p was identified as the target of hsa_circ_0001326. Meanwhile, p27 Kip1 was validated as the target of hsa_miR-186-5p. Moreover, the increased apoptosis and decreased migration induced by hsa_circ_0001326 OE were inhibited by p27 Kip1 knockdown. Hsa_circ_0001326 OE upregulated p27 Kip1 and cleaved caspase3 and downregulated CDK2 and cyclin E1 in cells, while these phenomena were reversed by p27 Kip1 knockdown. In addition, hsa_circ_0001326 OE induced G0/G1 cell cycle arrest was also attenuated in the presence of p27 Kip1 knockdown. Taken together, hsa_circ_0001326 OE contributed to the decreased viability of SWAN71 cells by targeting miR-186-5p via upregulation of p27 Kip1. Our findings were helpful to uncover the pathophysiological process of PE, as well as inspire the development of novel targeted therapy against PE. |
Databáze: | OpenAIRE |
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