LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes

被引：123
作者：
Yan, Jin [1 ,2 ]
Dang, Yini [1 ,2 ]
Liu, Shiyu [1 ,2 ,3 ]
Zhang, Yifeng [1 ,2 ]
Zhang, Guoxin [1 ,2 ]
机构：
[1] Nanjing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210000, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Clin Med Coll 1, Nanjing 210029, Jiangsu, Peoples R China
[3] 1 Peoples Hosp Xuzhou, Dept Gastroenterol, Xuzhou 221009, Jiangsu, Peoples R China
来源：
TUMOR BIOLOGY | 2016年 / 37卷 / 12期
基金：
中国国家自然科学基金;
关键词：
Gastric cancer; HOTAIR; miR-126; PI3K/AKT; Cisplatin resistance; LONG NONCODING RNA; OSTEOSARCOMA CELLS; DRUG-RESISTANCE; OVEREXPRESSION; GROWTH; EXPRESSION; PATHWAY;
D O I：
10.1007/s13277-016-5448-5
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.
引用
收藏
页码：16345 / 16355
页数：11
相关论文
共 34 条
[1]  
[Anonymous], ONCOGENE
[2]   Global identification of human transcribed sequences with genome tiling arrays [J].
Bertone, P ;
Stolc, V ;
Royce, TE ;
Rozowsky, JS ;
Urban, AE ;
Zhu, XW ;
Rinn, JL ;
Tongprasit, W ;
Samanta, M ;
Weissman, S ;
Gerstein, M ;
Snyder, M .
SCIENCE, 2004, 306 (5705) :2242-2246
[3]   A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA [J].
Cesana, Marcella ;
Cacchiarelli, Davide ;
Legnini, Ivano ;
Santini, Tiziana ;
Sthandier, Olga ;
Chinappi, Mauro ;
Tramontano, Anna ;
Bozzoni, Irene .
CELL, 2011, 147 (02) :358-369
[4]   A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1 [J].
Chang, Xiu-bao .
CANCER AND METASTASIS REVIEWS, 2007, 26 (01) :15-37
[5]   OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].
COLE, SPC ;
BHARDWAJ, G ;
GERLACH, JH ;
MACKIE, JE ;
GRANT, CE ;
ALMQUIST, KC ;
STEWART, AJ ;
KURZ, EU ;
DUNCAN, AMV ;
DEELEY, RG .
SCIENCE, 1992, 258 (5088) :1650-1654
[6]   Finishing the euchromatic sequence of the human genome [J].
Collins, FS ;
Lander, ES ;
Rogers, J ;
Waterston, RH .
NATURE, 2004, 431 (7011) :931-945
[7]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[8]   Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].
Gupta, Rajnish A. ;
Shah, Nilay ;
Wang, Kevin C. ;
Kim, Jeewon ;
Horlings, Hugo M. ;
Wong, David J. ;
Tsai, Miao-Chih ;
Hung, Tiffany ;
Argani, Pedram ;
Rinn, John L. ;
Wang, Yulei ;
Brzoska, Pius ;
Kong, Benjamin ;
Li, Rui ;
West, Robert B. ;
van de Vijver, Marc J. ;
Sukumar, Saraswati ;
Chang, Howard Y. .
NATURE, 2010, 464 (7291) :1071-U148
[9]   lincRNAs act in the circuitry controlling pluripotency and differentiation [J].
Guttman, Mitchell ;
Donaghey, Julie ;
Carey, Bryce W. ;
Garber, Manuel ;
Grenier, Jennifer K. ;
Munson, Glen ;
Young, Geneva ;
Lucas, Anne Bergstrom ;
Ach, Robert ;
Bruhn, Laurakay ;
Yang, Xiaoping ;
Amit, Ido ;
Meissner, Alexander ;
Regev, Aviv ;
Rinn, John L. ;
Root, David E. ;
Lander, Eric S. .
NATURE, 2011, 477 (7364) :295-U60
[10]   Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA [J].
Hayes, Erin L. ;
Lewis-Wambi, Joan S. .
BREAST CANCER RESEARCH, 2015, 17
1234