HOXD-AS1/miR-130a sponge regulates glioma development by targeting E2F8

被引:64
作者
Chen, Yinan [1 ,2 ]
Zhao, Fengbo [3 ]
Cui, Daming [4 ]
Jiang, Rui [1 ,2 ]
Chen, Jian [1 ,2 ]
Huang, Qingfeng [1 ,2 ]
Shi, Jinlong [1 ,2 ]
机构
[1] Nantong Univ, Affiliated Hosp, Jiangsu Clin Med Ctr Tissue Engn & Nerve Injury R, 20 Xisi Rde, Nantong 226001, Jiangsu, Peoples R China
[2] Nantong Univ, Affiliated Hosp, Dept Neurosurg, 20 Xisi Rde, Nantong 226001, Jiangsu, Peoples R China
[3] Nantong Univ, Med Sch, Basic Med Res Ctr, 19 Qixiu Rd, Nantong 226001, Jiangsu, Peoples R China
[4] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Neurosurg, Shanghai 200072, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
lncRNA; HOXD-AS1; E2F8; miR-130a; ceRNA; LONG NONCODING RNA; TRANSCRIPTION FACTORS; MICRORNA SPONGES; CANCER; EXPRESSION; PROLIFERATION; SUPPRESSES; HYPOTHESIS; MALIGNANCY; MIGRATION;
D O I
10.1002/ijc.31262
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioma development is an extremely complex process with changes occurring in numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1), an important long noncoding RNA (lncRNA), is known to regulate metastasis-related gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in human glioma cells. Our results proved that HOXD-AS1 expression was upregulated in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression repressed these cellular processes. Mechanistic studies further revealed that HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a, thus affecting E2F8 expression. Additionally, reciprocal repression was observed between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive effects of HOXD-AS1 knockdown. Taken together, these results provide a comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human glioma. What's new? Glioblastoma is one of the deadliest human cancers, and early diagnostic markers and new therapies are urgently needed. Here the authors found a long-noncoding RNA, HOXD-AS1, upregulated in human glioma. HOXD-AS1 is transcribed from the HOXD gene cluster in an antisense fashion and promoted glioma cell migration and invasion, a process reversed by the transcription factor E2F8. These results provide new mechanistic insight into glioma development and might help define new diagnostics or treatments for glioblastoma patients.
引用
收藏
页码:2313 / 2322
页数:10
相关论文
共 53 条
[1]   miR-20a regulates proliferation, differentiation and apoptosis in P19 cell model of cardiac differentiation by targeting Smoothened [J].
Ai, Feng ;
Zhang, Yanwei ;
Peng, Bangtian .
BIOLOGY OPEN, 2016, 5 (09) :1260-1265
[2]  
[Anonymous], J CELL BIOCH
[3]   The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144 [J].
Cai, Heng ;
Xue, Yixue ;
Wang, Ping ;
Wang, Zhenhua ;
Li, Zhen ;
Hu, Yi ;
Li, Zhiqing ;
Shang, Xiuli ;
Liu, Yunhui .
ONCOTARGET, 2015, 6 (23) :19759-19779
[4]   Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer [J].
Conte, Federica ;
Fiscon, Giulia ;
Chiara, Matteo ;
Colombo, Teresa ;
Farina, Lorenzo ;
Paci, Paola .
PLOS ONE, 2017, 12 (02)
[5]   MicroRNA miR-155 Is Necessary for Efficient Gammaherpesvirus Reactivation from Latency, but Not for Establishment of Latency [J].
Crepeau, Rebecca L. ;
Zhang, Peisheng ;
Usherwood, Edward J. .
JOURNAL OF VIROLOGY, 2016, 90 (17) :7811-7821
[6]   E2F8 Contributes to Human Hepatocellular Carcinoma via Regulating Cell Proliferation [J].
Deng, Qing ;
Wang, Qun ;
Zong, Wei-Ying ;
Zheng, Da-Li ;
Wen, Yi-Xin ;
Wang, Ke-Sheng ;
Teng, Xiao-Mei ;
Zhang, Xin ;
Huang, Jian ;
Han, Ze-Guang .
CANCER RESEARCH, 2010, 70 (02) :782-791
[7]   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
[8]   Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways [J].
Ergun, Sercan ;
Oztuzcu, Serdar .
TUMOR BIOLOGY, 2015, 36 (05) :3129-3136
[9]  
Fatima Roshan, 2015, Mol Cell Ther, V3, P5
[10]   RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts [J].
Geisler, Sarah ;
Coller, Jeff .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (11) :699-712