LncRNA HOTAIR acts as competing endogenous RNA to control the expression of Notch3 via sponging miR-613 in pancreatic cancer

被引:97
作者
Cai, Huihua [1 ]
Yao, Jie [2 ]
An, Yong [1 ]
Chen, Xuemin [1 ]
Chen, Weibo [1 ]
Wu, Di [1 ]
Luo, Boyang [1 ]
Yang, Yong [1 ]
Jiang, Yong [1 ]
Sun, Donglin [1 ]
He, Xiaozhou [3 ]
机构
[1] Soochow Univ, Hosp 3, Peoples Hosp Changzhou 1, Dept Hepatobiliary Surg, Changzhou, Jiangsu, Peoples R China
[2] Yangzhou Univ, Dept Hepatobiliary & Pancreat Surg, Northern Jiangsu Peoples Hosp, Clin Med Coll, Yangzhou, Jiangsu, Peoples R China
[3] Soochow Univ, Hosp 3, Peoples Hosp Changzhou 1, Dept Urol, Changzhou, Jiangsu, Peoples R China
关键词
pancreatic cancer; miR-613; HOTAIR; cell proliferation; invasion and migration; LONG NONCODING RNAS; CELL-PROLIFERATION; PROGNOSTIC BIOMARKER; CLIP-SEQ; INVASION; PROGRESSION; MICRORNAS; INHIBITION; RESISTANCE; MIGRATION;
D O I
10.18632/oncotarget.16462
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.
引用
收藏
页码:32905 / 32917
页数:13
相关论文
共 39 条
[1]   Regulation of multidrug resistance by microRNAs in anti-cancer therapy [J].
An, Xin ;
Sarmiento, Cesar ;
Tan, Tao ;
Zhu, Hua .
ACTA PHARMACEUTICA SINICA B, 2017, 7 (01) :38-51
[2]   Long noncoding RNAs in cancer: mechanisms of action and technological advancements [J].
Bartonicek, Nenad ;
Maag, Jesper L. V. ;
Dinger, Marcel E. .
MOLECULAR CANCER, 2016, 15
[3]   Epigenetic inhibition of miR-663b by long non-coding RNA HOTAIR promotes pancreatic cancer cell proliferation via up-regulation of insulin-like growth factor 2 [J].
Cai, Huihua ;
An, Yong ;
Chen, Xuemin ;
Sun, Donglin ;
Chen, Tongbing ;
Peng, Yan ;
Zhu, Feng ;
Jiang, Yong ;
He, Xiaozhou .
ONCOTARGET, 2016, 7 (52) :86857-86870
[4]   MiR-377 inhibits the proliferation of pancreatic cancer by targeting Pim-3 [J].
Chang, Weihua ;
Liu, Menggang ;
Xu, Jianhua ;
Fu, Hangwei ;
Zhou, Bo ;
Yuan, Tao ;
Chen, Ping .
TUMOR BIOLOGY, 2016, 37 (11) :14813-14824
[5]   Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer [J].
Chen, Xu ;
Xu, Yanmei ;
Liao, Xingyun ;
Liao, Rongxia ;
Zhang, Luping ;
Niu, Kai ;
Li, Tao ;
Li, Dezhi ;
Chen, Zhengtang ;
Duan, Yuzhong ;
Sun, Jianguo .
TUMOR BIOLOGY, 2016, 37 (09) :11927-11936
[6]  
Coveler Andrew L, 2016, Am Soc Clin Oncol Educ Book, V35, pe217, DOI 10.14694/EDBK_160827
[7]   Nutrition, microRNAs, and Human Health [J].
Cui, Juan ;
Zhou, Beiyan ;
Ross, Sharon A. ;
Zempleni, Janos .
ADVANCES IN NUTRITION, 2017, 8 (01) :105-112
[8]  
Fan Y, 2017, AM J CANCER RES, V7, P139
[9]   MicroRNAs in Human Cancer [J].
Farazi, Thalia A. ;
Hoell, Jessica I. ;
Morozov, Pavel ;
Tuschl, Thomas .
MICRORNA CANCER REGULATION: ADVANCED CONCEPTS, BIOINFORMATICS AND SYSTEMS BIOLOGY TOOLS, 2013, 774 :1-20
[10]   A Multidisciplinary Approach to Pancreas Cancer in 2016: A Review [J].
Fogel, Evan L. ;
Shahda, Safi ;
Sandrasegaran, Kumar ;
DeWitt, John ;
Easler, Rey J. ;
Agarwal, David M. ;
Eagleson, Mackenzie ;
Zyromski, Nicholas J. ;
House, Michael G. ;
Ellsworth, Susannah ;
El Hajj, Ihab ;
O'Neil, Bert H. ;
Nakeeb, Attila ;
Sherman, Stuart .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2017, 112 (04) :537-554