title: Knockdown of BMI-1 causes cell-cycle arrest and derepresses p16INK4a, HOXA9 and HOXC13 mRNA expression in HeLa cells.
abstract: The human oncogene B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a member of the mammalian Polycomb group family. The overexpression of BMI-1 is associated with human malignancies. In this study, the effects of knockdown of BMI-1 by shRNA-mediated RNA interference on cell cycle and possible downstream targets in human cervical adenocarcinoma HeLa cells were investigated. As a result, when the shRNA plasmid was stably introduced into the cell line, the mRNA and protein of BMI-1 were specifically down-regulated, and the cells increased in the phase of G1 and cells in S phase significantly decreased by flow cytometric analysis; the knockdown of BMI-1 expression could lead to significant up-regulation of p16INK4a, HOXA9 and HOXC13 mRNA expression, but hTERT and HOXB4 mRNA expression did not change significantly. In conclusion, RNAi-mediated knockdown of BMI-1 expression can induce cell-cycle arrest and up-regulate p16INK4a, HOXA9 and HOXC13 in HeLa cells. Our results suggest that targeting BMI-1 might be a therapeutic potential for the treatment of cancer.
authors.affiliation: Laboratory Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1277#, 430022, Wuhan, Hubei, People's Republic of China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Chen
authors.forename: Yirong
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002469:Cell Separation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C410305:HOXC13 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C097899:homeobox protein HOXA9; D063150:Polycomb Repressive Complex 1