MiR-141 Inhibits Gastric Cancer Proliferation by Interacting with Long Noncoding RNA MEG3 and Down-Regulating E2F3 Expression

被引:65
作者
Zhou, Xiaoying [1 ,2 ]
Ji, Guoping [1 ,2 ]
Ke, Xiquan [3 ]
Gu, Huiyuan [4 ]
Jin, Wujuan [1 ,2 ]
Zhang, Guoxin [1 ,2 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Clin Med Coll 1, Nanjing 210029, Jiangsu, Peoples R China
[3] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Xian 710061, Shanxi, Peoples R China
[4] Soochow Univ, Affiliated Hosp 1, Dept Gastroenterol, Suzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
MiR-141; MEG3; Cell growth; Cell cycle; Gastric cancer; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; PROMOTES; TRANSITION; INVASION;
D O I
10.1007/s10620-015-3782-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
MiR-141 and long noncoding RNA MEG3 have been independently reported to be tumor suppressor genes in various cancers. However, their expression has never been previously associated with gastric cancer (GC). To investigate the interaction of miR-141 and MEG3 in GC. QRT-PCR was used to detect miR-141, MEG3, and E2F3 in gastric tissues and cells. CCK-8 and flow cytometry analysis were used to detect cell functions. Western blot and luciferase activity were used to identify E2F3 as one of the direct targets of miR-141. We found that expression of both miR-141 and MEG3 was significantly reduced in GC compared with levels in matched nonmalignant tissues. Positive correlation between miR-141 and MEG3 was found in both tumor tissues and control tissues. Furthermore, the over-expression of either miR-141 or MEG3 in 7901 and MKN45 cells inhibited cell proliferation and cell cycle progression and promoted cell apoptosis. E2F3 was identified as a target of miR-141, and its inhibition significantly reduced MEG3 expression. E2F3 expression was also found to be negatively associated with both MEG3 and miR-141. E2F3 over-expression partly reversed the changes caused by transfection of miR-141 mimic, and inhibition of miR-141 or MEG3 overrides MEG3- or miR-141-induced modulation of cell growth in GC. These findings together suggested that miR-141 could be interacting with MEG3 and targeting E2F3, and these factors may play important anti-tumor effects in GC pathogenesis and provide therapeutic targets in the clinics.
引用
收藏
页码:3271 / 3282
页数:12
相关论文
共 27 条
[1]   The Cyclin-dependent Kinase Inhibitor p16INK4a Physically Interacts with Transcription Factor Sp1 and Cyclin-dependent Kinase 4 to Transactivate MicroRNA-141 and MicroRNA-146b-5p Spontaneously and in Response to Ultraviolet Light-induced DNA Damage [J].
Al-Khalaf, Huda H. ;
Mohideen, Peer ;
Nallar, Shreeram C. ;
Kalvakolanu, Dhananjaya V. ;
Aboussekhra, Abdelilah .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (49) :35511-35525
[2]   Loss of Imprinting and Allelic Switching at the DLK1-MEG3 Locus in Human Hepatocellular Carcinoma [J].
Anwar, Sumadi Lukman ;
Krech, Till ;
Hasemeier, Britta ;
Schipper, Elisa ;
Schweitzer, Nora ;
Vogel, Arndt ;
Kreipe, Hans ;
Lehmann, Ulrich .
PLOS ONE, 2012, 7 (11)
[3]  
Arita T, 2013, ANTICANCER RES, V33, P3185
[4]   microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer [J].
Braconi, C. ;
Kogure, T. ;
Valeri, N. ;
Huang, N. ;
Nuovo, G. ;
Costinean, S. ;
Negrini, M. ;
Miotto, E. ;
Croce, C. M. ;
Patel, T. .
ONCOGENE, 2011, 30 (47) :4750-4756
[5]   E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3 [J].
Chen, D. ;
Chen, Y. ;
Forrest, D. ;
Bremner, R. .
CELL DEATH AND DIFFERENTIATION, 2013, 20 (07) :931-940
[6]   Review article: the epidemiology and prevention of gastric cancer [J].
Fock, K. M. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2014, 40 (03) :250-260
[7]   MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis [J].
Hur, Keun ;
Toiyama, Yuji ;
Takahashi, Masanobu ;
Balaguer, Francesc ;
Nagasaka, Takeshi ;
Koike, Junichi ;
Hemmi, Hiromichi ;
Koi, Minoru ;
Boland, C. Richard ;
Goel, Ajay .
GUT, 2013, 62 (09) :1315-1326
[8]   Opposing Regulation of Sox2 by Cell-Cycle Effectors E2f3a and E2f3b in Neural Stem Cells [J].
Julian, Lisa M. ;
Vandenbosch, Renaud ;
Pakenham, Catherine A. ;
Andrusiak, Matthew G. ;
Nguyen, Angela P. ;
McClellan, Kelly A. ;
Svoboda, Devon S. ;
Lagace, Diane C. ;
Park, David S. ;
Leone, Gustavo ;
Blais, Alexandre ;
Slack, Ruth S. .
CELL STEM CELL, 2013, 12 (04) :440-452
[9]   MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways [J].
Li, X. ;
Roslan, S. ;
Johnstone, C. N. ;
Wright, J. A. ;
Bracken, C. P. ;
Anderson, M. ;
Bert, A. G. ;
Selth, L. A. ;
Anderson, R. L. ;
Goodall, G. J. ;
Gregory, P. A. ;
Khew-Goodall, Y. .
ONCOGENE, 2014, 33 (31) :4077-4088
[10]   Epigenetic Regulation of microRNAs in Gastric Cancer [J].
Ma, Jiaojiao ;
Hong, Liu ;
Chen, Zheng ;
Nie, Yongzhan ;
Fan, Daiming .
DIGESTIVE DISEASES AND SCIENCES, 2014, 59 (04) :716-723