HistoneH3 demethylase JMJD2A promotes growth of liver cancer cells through up-regulating miR372
| Autor: | Xin Gui, Xiaoru Xin, Zhuojia Lin, Jiao Li, Hu Pu, Jiahui An, Dongdong Lu, Qidi Zheng, Song Jia, Mengying Wu, Xiaonan Li, Yanan Lu, Yuxin Yang, Tianming Li, Jie Xu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 Male Transcriptional Activation Jumonji Domain-Containing Histone Demethylases Histone lysine methylation Ubiquitin-Protein Ligases PIM1 HistoneH3 demethylase JMJD2A Models Biological Epigenesis Genetic liver cancer Fungal Proteins 03 medical and health sciences Mice Transcription (biology) Cell Line Tumor medicine Animals Humans Promoter Regions Genetic Cell Proliferation Gene knockdown biology miR372 Cyclin-dependent kinase 2 Cell Cycle Cyclin-Dependent Kinase 2 Liver Neoplasms Cell cycle medicine.disease Gene Expression Regulation Neoplastic Pim1 Disease Models Animal MicroRNAs Retinoblastoma Binding Proteins 030104 developmental biology Oncology Immunology Cancer research biology.protein Demethylase Heterografts biological phenomena cell phenomena and immunity Mitogen-Activated Protein Kinases Liver cancer P21WAF1/Cip1 Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Jiahui An 1 , Jie Xu 1 , Jiao Li 2 , Song Jia 2 , Xiaonan Li 1 , Yanan Lu 1 ,Yuxin Yang 1 , Zhuojia Lin 1 , Xiaoru Xin 1 , Mengying Wu 1 , Qidi Zheng 1 , Hu Pu 1 , Xin Gui 1 , Tianming Li 1 and Dongdong Lu 1 1 School of Life Science and Technology, Tongji University, Shanghai, 20092, China 2 School of Medicine, Tongji University, Shanghai, 200092, China Correspondence to: Dongdong Lu, email: ludongdong@tongji.edu.cn Keywords: liver cancer, HistoneH3 demethylase JMJD2A, miR372, P21WAF1/Cip1, Pim1 Received: October 07, 2016 Accepted: April 01, 2017 Published: April 13, 2017 ABSTRACT Changes in histone lysine methylation status have been observed during cancer formation. JMJD2A protein is a demethylase that is overexpressed in several tumors. Herein, our results demonstrate that JMJD2A accelerates malignant progression of liver cancer cells in vitro and in vivo . Mechanistically, JMJD2A promoted the expression and mature of pre-miR372 epigenetically. Notably, miR372 blocks the editing of 13th exon-introns-14th exon and forms a novel transcript( JMJD2AΔ) of JMJD2A. In particular, JMJD2A inhibited P21(WAF1/Cip1) expression by decreasing H3K9me3 dependent on JMJD2AΔ. Thereby, JMJD2A could enhance Pim1 transcription by suppressing P21(WAF1/Cip1). Furthermore, through increasing the expression of Pim1, JMJD2A could facilitate the interaction among pRB, CDK2 and CyclinE which prompts the transcription and translation of oncogenic C-myc. Strikingly, JMJD2A may trigger the demethylation of Pim1. On the other hand, Pim1 knockdown and P21(WAF1/Cip1) overexpression fully abrogated the oncogenic function of JMJD2A. Our observations suggest that JMJD2A promotes liver cancer cell cycle progress through JMJD2A-miR372-JMJD2AΔ-P21WAF1/Cip1-Pim1-pRB-CDK2-CyclinE-C-myc axis. This study elucidates a novel mechanism for JMJD2A in liver cancer cells and suggests that JMJD2A can be used as a novel therapeutic targets of liver cancer. |
| Databáze: | OpenAIRE |
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