INMAP Overexpression Inhibits Cell Proliferation, Induces Genomic Instability and Functions through p53/p21 Pathways
| العنوان: | INMAP Overexpression Inhibits Cell Proliferation, Induces Genomic Instability and Functions through p53/p21 Pathways |
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| المؤلفون: | Tan Tan, Yan-Bo Zheng, Qianjin Liang, Yan Lei, Le Sun, Baochen Du, Xiangfeng Lu, Yan Zhu, Jingting Kang |
| المصدر: | PLoS ONE PLoS ONE, Vol 10, Iss 1, p e0115704 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cyclin-Dependent Kinase Inhibitor p21, DNA damage, Cell, lcsh:Medicine, Cell Cycle Proteins, Spindle Apparatus, Biology, Genomic Instability, Histones, Mice, Downregulation and upregulation, medicine, Animals, Humans, lcsh:Science, Mitosis, Cell Proliferation, Multidisciplinary, Cell growth, lcsh:R, Nuclear Proteins, Xenograft Model Antitumor Assays, Molecular biology, Spindle apparatus, medicine.anatomical_structure, Gene Expression Regulation, Apoptosis, Cell culture, lcsh:Q, Tumor Suppressor Protein p53, HeLa Cells, Signal Transduction, Research Article |
| الوصف: | INMAP is a spindle protein that plays essential role for mitosis, by ensuring spindle and centromere integrality. The aim of this study was to investigate the relevant functions of INMAP for genomic stability and its functional pathway. We overexpressed INMAP in HeLa cells, resulting in growth inhibition in monolayer cell cultures, anchorage-independent growth in soft agar and xenograft growth in nude mice. In this system caused micronuclei (MNi) formation, chromosome distortion and γH2AX expression upregulation, suggesting DNA damage induction and genomic stability impairment. As a tumour biochemical marker, lactate dehydrogenase (LDH) isoenzymes were detected to evaluate cell metabolic activity, the results confirming that total activity of LDH, as well as that of its LDH5 isoform, is significantly decreased in INMAP-overexpressing HeLa cells. The levels of p53 and p21 were upregulated, and however, that of PCNA and Bcl-2, downregulated. Indirect immunofluorescence (IIF) and coimmunoprecipitation (CoIP) analyses revealed the interaction between INMAP and p21. These results suggest that INMAP might function through p53/p21 pathways. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd43eb93af98710a9bdb211ab9f7a95e https://doi.org/10.1371/journal.pone.0115704 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fd43eb93af98710a9bdb211ab9f7a95e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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