Long non-coding RNA H19 mediates ovarian cancer cell cisplatin-resistance and migration during EMT

被引:8
作者
Wu, Yuxian [1 ]
Zhou, Yang [1 ]
He, Jie [1 ]
Sun, Hao [1 ]
Jin, Zhijun [1 ]
机构
[1] Naval Mil Med Univ, Dept Obstet & Gynaecol, Changzheng Hosp, 415 Fengyang Rd, Shanghai 200003, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2019年 / 12卷 / 07期
关键词
Ovarian cancer; lncRNA H19; cisplatin-resistance; migration; EMT; EPITHELIAL-MESENCHYMAL TRANSITION; EXPRESSION; SNAIL; TWIST; SLUG; CARCINOMA; REGULATORS; CADHERIN;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: (1) to investigate the expression of long non-coding RNA (lncRNA) H19 in OVCAR3 and cisplatin-resistant OVCAR3/DDP cells; (2) to explore the effects of lncRNA H19 on cisplatin-resistance in ovarian cancer (OC) cells; (3) to determine the roles of lncRNA H19 on OC cell migration and epithelial to mesenchymal transition (EMT)-related factors. Methods: The human ovarian cancer OVCAR3 cell line was obtained from ATCC; the cisplatinresistant OVCAR3/DDP cell line was induced from OVCAR3 cells through a progressive cisplatin concentration; OVCAR3 cells that overexpress lncRNA H19 and OVCAR3/DDP cells that silence the lncRNA H19 expression were established by the transfection of a recombinant lentivirus. A cell counting kit-8 (CCK-8) assay was used to determine the cell viability of OVCAR3 and OVCAR3/DDP. A reverse transcription-quantitative polymerase chain reaction (RT-qPCR) demonstrated the expressions of lncRNA H19, E-cadherin, twist, slug, and snail mRNA in OVCAR3 and OVCAR3/DDP cells. A Transwell assay was used to investigate the migration of OVCAR3 and OVCAR3/DDP cells. The expressions of E-cadherin, twist, slug, and snail proteins were determined by Western blot. Results: The cisplatinresistant OVCAR3/DPP cells were successfully established. The level of lncRNA H19 in the OVCAR3/DDP cells was significantly elevated compared with the OVCAR3 cells (P <0.05). The overexpression of lncRNA in the OVCAR3 cells improved the cisplatin-resistance, and the inhibition of lncRNA H19 expression in OVCAR3/DDP cells eliminated the cisplatin resistance. Furthermore, the migration ability and the expressions of the EMT positive regulator, twist, slug, snail mRNA, and protein in OVCAR3/DDP were dramatically up-regulated compared with the OVCAR3 group, and the expressions of the EMT negative regulator, E-cadherin mRNA, and protein were decreased compared with the OVCAR3 group, suggesting an increase of migration and EMT ability was observed in the OVCAR3/DDP cells. A gain of lncRNA expression in the OVCAR3 cells promoted migration and EMT-related activity; the loss of lncRNA H19 expression eliminated the enhanced ability of migration and EMT in the OVCAR3/DDP cells. Conclusions: LncRNA H19 is responsible for the cisplatin-resistance, migration, and MET regulation in OVCAR3 cells.
引用
收藏
页码:2506 / 2515
页数:10
相关论文
共 31 条
[1]   N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1 [J].
Alexander, NR ;
Tran, NL ;
Rekapally, H ;
Summers, CE ;
Glackin, C ;
Heimark, RL .
CANCER RESEARCH, 2006, 66 (07) :3365-3369
[2]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[3]   The biology of ovarian cancer: new opportunities for translation [J].
Bast, Robert C., Jr. ;
Hennessy, Bryan ;
Mills, Gordon B. .
NATURE REVIEWS CANCER, 2009, 9 (06) :415-428
[4]   Cancer of the ovary [J].
Cannistra, SA .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (24) :2519-2529
[5]   Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer [J].
Cao, L. ;
Shao, M. ;
Schilder, J. ;
Guise, T. ;
Mohammad, K. S. ;
Matei, D. .
ONCOGENE, 2012, 31 (20) :2521-2534
[6]   Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Colombo, N. ;
Peiretti, M. ;
Parma, G. ;
Lapresa, M. ;
Mancari, R. ;
Carinelli, S. ;
Sessa, C. ;
Castiglione, M. .
ANNALS OF ONCOLOGY, 2010, 21 :v23-v30
[7]   Epithelial mesenchymal transition in ovarian carcinoma [J].
Davidson, Ben ;
Trope, Claes G. ;
Reich, Reuven .
FRONTIERS IN ONCOLOGY, 2012, 2
[8]   From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis [J].
Dhamija, Sonam ;
Diederichs, Sven .
INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (02) :269-280
[9]   A review of the current evidence for maintenance therapy in ovarian cancer [J].
Foster, Talia ;
Brown, T. Michelle ;
Chang, Jane ;
Menssen, Hans D. ;
Blieden, Marissa B. ;
Herzog, Thomas J. .
GYNECOLOGIC ONCOLOGY, 2009, 115 (02) :290-301
[10]  
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, 2016, Lancet, V388, P1545, DOI 10.1016/S0140-6736(16)31678-6