Hypermethylated long noncoding RNA MEG3 promotes the progression of gastric cancer

被引:34
作者
Ding, Lei [1 ]
Tian, Yuan [2 ]
Wang, Ling [3 ]
Bi, Miaomiao [4 ]
Teng, Dengke [5 ]
Hong, Sen [6 ]
机构
[1] Jilin Univ, Dept Radiol, China Japan Union Hosp, Changchun 130022, Jilin, Peoples R China
[2] Jilin Univ, Dept Med Examinat, China Japan Union Hosp, Changchun 130022, Jilin, Peoples R China
[3] Second Hosp Jilin Univ, Dept Gynecol & Obstet, Changchun 130041, Jilin, Peoples R China
[4] Jilin Univ, Dept Ophthalmol, China Japan Union Hosp, Changchun 130022, Jilin, Peoples R China
[5] Jilin Univ, Dept Ultrasonog, China Japan Union Hosp, Changchun 130022, Jilin, Peoples R China
[6] First Hosp Jilin Univ, Dept Colorectal & Anal Surg, Changchun 130000, Jilin, Peoples R China
来源
AGING-US | 2019年 / 11卷 / 19期
关键词
gastric cancer; methylation; MEG3; miR-181a-5p; ATP4B; GENE-EXPRESSION; DNA METHYLATION; MICRORNA-181A-5P; PROLIFERATION; CELLS;
D O I
10.18632/aging.102309
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
This study aims to explore the expression and degree of methylation of lncRNA MEG3 in gastric cancer tissues and to analyze its effect on the migration and proliferation of gastric cancer patients and the mechanism by which this occurs. The targeting relationship between MEG3, miR-181a-5p and ATP4B was detected through molecular biology experiments. Wound healing, transwell, colony formation and flow cytometry assays were used to analyze the effects of lncRNA MEG3 and methylation on tumor cell migration, invasion, proliferation and apoptosis. In addition, a tumor xenotransplantation model was established to study the influence of MEG3 on tumor growth in vivo. Bioinformatics analysis showed that lncRNA MEG3 and ATP4B were downregulated in gastric cancer tissues compared with normal tissues. Bioinformatics predicted that ATP4B might be regulated by targeting miR-181a-5p. The overexpression of MEG3 and the application of 5-Aza treatment inhibited the migration, invasion and proliferation of MGC-803 cells and promoted apoptosis. In gastric cancer tissues, MEG3 is hypermethylated to decrease expression. Once the expression of MEG3 is restored or methylation is inhibited, tumor growth can be inhibited both in vivo and in vitro. This finding could be utilized as a clinical reference for gastric cancer treatment in the future.
引用
收藏
页码:8139 / 8155
页数:17
相关论文
共 38 条
[1]   Effects of dexamethasone and Mycoplasma bovis on bovine neutrophil function in vitro [J].
Alabdullah, Hussain A. ;
Fox, Lawrence K. ;
Gay, John M. ;
Barrington, George M. ;
Mealey, Robert H. .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2015, 164 (1-2) :67-73
[2]   DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: Its possible involvement in the formation of epigenetic field defect [J].
Ando, Takayuki ;
Yoshida, Takeichi ;
Enomoto, Shotaro ;
Asada, Kiyoshi ;
Tatematsu, Masae ;
Ichinose, Masao ;
Sugiyama, Toshiro ;
Ushijima, Toshikazu .
INTERNATIONAL JOURNAL OF CANCER, 2009, 124 (10) :2367-2374
[3]   Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa [J].
Arisawa, Tomiyasu ;
Tahara, Tomomitsu ;
Tsutsumi, Mikihiro ;
Shibata, Tomoyuki .
BMC MEDICAL GENETICS, 2012, 13
[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]   The long non-coding RNA ANRASSF1 in the regulation of alternative protein-coding transcripts RASSF1A and RASSF1C in human breast cancer cells: implications to epigenetic therapy [J].
Calanca, Naiade ;
Paschoal, Ana Paula ;
Munhoz, Erika Prando ;
Galindo, Layla Testa ;
Barbosa, Barbara Mitsuyasu ;
Figaro Caldeira, Jose Roberto ;
Oliveira, Rogerio Antonio ;
Cavalli, Luciane Regina ;
Rogatto, Silvia Regina ;
Rainho, Claudia Aparecida .
EPIGENETICS, 2019, 14 (08) :741-750
[6]  
Cao BP, 2016, DISCOV MED, V21, P159
[7]   RETRACTED: MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1 (Retracted article. See vol. 57, pg. 311, 2023) [J].
Cao, Yang ;
Zhao, Dan ;
Li, Ping ;
Wang, Lanrong ;
Qiao, Bingli ;
Qin, Xiaoyan ;
Li, Lei ;
Wang, Yang .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 42 (01) :346-356
[8]   Global DNA hypomethylation is an early event in Helicobacter pylori-related gastric carcinogenesis [J].
Compare, Debora ;
Rocco, Alba ;
Liguori, Eleonora ;
D'Armiento, Francesco Paolo ;
Persico, Giovanni ;
Masone, Stefania ;
Coppola-Bottazzi, Enrico ;
Suriani, Renzo ;
Romano, Marco ;
Nardone, Gerardo .
JOURNAL OF CLINICAL PATHOLOGY, 2011, 64 (08) :677-682
[9]   LncRNA-MEG3 inhibits proliferation and metastasis by regulating miRNA-21 in gastric cancer [J].
Dan, Jie ;
Wang, Jian ;
Wang, Yonghong ;
Zhu, Mingjie ;
Yang, Xiaojun ;
Peng, Zhong ;
Jiang, Hongyuan ;
Chen, Lei .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 99 :931-938
[10]   Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance [J].
Danza, Katia ;
Silvestris, Nicola ;
Simone, Giovanni ;
Signorile, Michele ;
Saragoni, Luca ;
Brunetti, Oronzo ;
Monti, Manlio ;
Mazzotta, Annalisa ;
De Summa, Simona ;
Mangia, Anita ;
Tommasi, Stefania .
CANCER BIOLOGY & THERAPY, 2016, 17 (04) :400-406