MiR-183/-96/-182 cluster is up-regulated in most breast cancers and increases cell proliferation and migration

被引：149
作者：
Li, Pei [1 ]
Sheng, Cheng [1 ]
Huang, Lingling [1 ]
Zhang, Hui [2 ]
Huang, Lihua [2 ]
Cheng, Zeneng [1 ]
Zhu, Qubo [1 ]
机构：
[1] Cent S Univ, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China
来源：
BREAST CANCER RESEARCH | 2014年 / 16卷 / 06期
基金：
中国国家自然科学基金;
关键词：
TRANSCRIPTION FACTOR; DOWN-REGULATION; EXPRESSION; MICRORNA; MIR-182; METASTASIS; ZEB1; TUMORIGENICITY; CYTOKINESIS; ACTIVATION;
D O I：
10.1186/s13058-014-0473-z
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Introduction: The miR-183/-96/-182 cluster is a conserved polycistronic microRNA (miRNA) cluster which is highly expressed in most breast cancers. Although there are some sporadic reports which demonstrate the importance of each miRNA in this cluster in breast cancer, the biological roles of this cluster as a whole and its regulation mechanisms in breast cancer are still unclear. We compared the expression of this cluster in different cancer types, analyzed the regulation mechanism of this cluster, identified new target genes, and examined the impact of this cluster on breast cancer cells. Methods: The miRNA level was detected by LNA-based northern blot and Real-time PCR, and was also analyzed from TCGA dataset. Bioinformatics research and luciferase assay were applied to find the promoter regions and transcription factors. To investigate the biological effects of the miR-183/-96 /-182 cluster in breast cancer, we generated miR-96, miR-182 and miR-183 overexpression stable cell lines to check the overdose effects; we also used miR-Down (TM) antagomir for each miRNA as well as miR-183/-96 /-182 cluster sponge lentivirus to check the knockdown effects. Growth, migration, cell cycle profile and survival of these cells was then monitored by colony formation assay, MTT assay, cell wound healing assay, flow cytometry and microscopy. The target gene was validated by Real-time PCR, luciferase assay, Western blot and Phalloidin/DAPI counterstaining. Results: The miR-183/-96/-182 cluster was highly expressed in most breast cancers, and its transcription is disordered in breast cancer. The miR-183/-96/-182 cluster was transcribed in the same pri-miRNA and its transcription was regulated by ZEB1 and HSF2. It increased breast cell growth by promoting more rapid completion of mitosis, promoted cell migration and was essential for cell survival. MiR-183 targeted the RAB21 mRNA directly in breast cancer. Conclusion: The miR-183/-96/-182 cluster is up-regulated in most breast cancer. It functions as an oncogene in breast cancer as it increases cell proliferation and migration.
引用
收藏
页数：17
相关论文
共 38 条
[1]   Poised Chromatin at the ZEB1 Promoter Enables Breast Cancer Cell Plasticity and Enhances Tumorigenicity [J].
Chaffer, Christine L. ;
Marjanovic, Nemanja D. ;
Lee, Tony ;
Bell, George ;
Kleer, Celina G. ;
Reinhardt, Ferenc ;
D'Alessio, Ana C. ;
Young, Richard A. ;
Weinberg, Robert A. .
CELL, 2013, 154 (01) :61-74
[2]   Up-regulation of miR-182 by β-catenin in breast cancer increases tumorigenicity and invasiveness by targeting the matrix metalloproteinase inhibitor RECK [J].
Chiang, Chi-Hsiang ;
Hou, Ming-Feng ;
Hung, Wen-Chun .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2013, 1830 (04) :3067-3076
[3]   Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data [J].
Chien, Chia-Hung ;
Sun, Yi-Ming ;
Chang, Wen-Chi ;
Chiang-Hsieh, Pei-Yun ;
Lee, Tzong-Yi ;
Tsai, Wei-Chih ;
Horng, Jorng-Tzong ;
Tsou, Ann-Ping ;
Huang, Hsien-Da .
NUCLEIC ACIDS RESEARCH, 2011, 39 (21) :9345-9356
[4]   Transcriptional activation by the zinc-finger homeodomain protein δEF1 in estrogen signaling cascades [J].
Dillner, NB ;
Sanders, MM .
DNA AND CELL BIOLOGY, 2004, 23 (01) :25-34
[5]   MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells [J].
Ebert, Margaret S. ;
Neilson, Joel R. ;
Sharp, Phillip A. .
NATURE METHODS, 2007, 4 (09) :721-726
[6]   Reciprocal regulation of ZEB1 and AR in triple negative breast cancer cells [J].
Graham, Tisheeka R. ;
Yacoub, Rami ;
Taliaferro-Smith, LaTonia ;
Osunkoya, Adeboye O. ;
Odero-Marah, Valerie A. ;
Liu, Tongrui ;
Kimbro, K. Sean ;
Sharma, Dipali ;
O'Regan, Ruth M. .
BREAST CANCER RESEARCH AND TREATMENT, 2010, 123 (01) :139-147
[7]   Mammalian microRNAs predominantly act to decrease target mRNA levels [J].
Guo, Huili ;
Ingolia, Nicholas T. ;
Weissman, Jonathan S. ;
Bartel, David P. .
NATURE, 2010, 466 (7308) :835-U66
[8]   Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells [J].
Guttilla, Irene K. ;
White, Bruce A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (35) :23204-23216
[9]   Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer [J].
Hannafon, Bethany N. ;
Sebastiani, Paola ;
de las Morenas, Antonio ;
Lu, Jining ;
Rosenberg, Carol L. .
BREAST CANCER RESEARCH, 2011, 13 (02)
[10]   Cytokinesis failure due to derailed integrin traffic induces aneuploidy and oncogenic transformation in vitro and in vivo [J].
Hognas, G. ;
Tuomi, S. ;
Veltel, S. ;
Mattila, E. ;
Murumagi, A. ;
Edgren, H. ;
Kallioniemi, O. ;
Ivaska, J. .
ONCOGENE, 2012, 31 (31) :3597-3606
1234