title: INMAP overexpression inhibits cell proliferation, induces genomic instability and functions through p53/p21 pathways.
abstract: 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.
authors: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Yan
authors: Y
authors: Zhu
authors: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Yan
authors: Y
authors: Lei
authors: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Baochen
authors: B
authors: Du
authors: The Institute of Medical Biotechnology (IMB) of the Chinese Academy of Medical Sciences, Beijing, 100050, P. R. China.
authors: Yanbo
authors: Y
authors: Zheng
authors: Dongzhimen Hospital of Beijing University of Chinese Traditional Medicine, Beijing, 100700, P. R. China.
authors: Xiangfeng
authors: X
authors: Lu
authors: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Tan
authors: T
authors: Tan
authors: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Jingting
authors: J
authors: Kang
authors: AbMax Biotechnology Co., Haidian, Beijing, 100085, P. R. China.
authors: Le
authors: L
authors: Sun
authors: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, 100875, P. R. China.
authors: Qianjin
authors: Q
authors: Liang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006367:HeLa Cells; D006657:Histones / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones; C540368:INMAP protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53
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