LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs

被引:65
作者
Zhang, Yanshan [1 ]
Chen, Weizuo [1 ]
Pan, Tingting [1 ]
Wang, Huijuan [2 ]
Zhang, Yinguo [3 ]
Li, Chao [3 ]
机构
[1] Tumor Hosp Wuwei, Dept Radiotherapy, Wuwei 733000, Gansu, Peoples R China
[2] Tumor Hosp Wuwei, Dept Tumor Chemotherapy, Wuwei 733000, Gansu, Peoples R China
[3] Tumor Hosp Wuwei, Dept Thorac Surg, Wuwei 733000, Gansu, Peoples R China
关键词
LBX2-AS1; ESCC; Migration; HNRNPC; ZEB1; TO-MESENCHYMAL TRANSITION; LONG NONCODING RNAS; CANCER STATISTICS; PROTEIN; EXPRESSION; PROLIFERATION; APOPTOSIS; GROWTH; CHINA; GENE;
D O I
10.1016/j.bbrc.2019.02.079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long non-coding RNAs (lncRNAs) are a group of transcripts, which can regulate the progression of esophageal squamous cell carcinoma (ESCC). According to the data of TCGA, Ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) is a highly expressed lncRNA in ESCC samples. Herein, we chose it for further study. Furtherly, dysregulation of LBX2-AS1 was identified in ESCC tissues with metastasis. Loss-of function assays were conducted and revealed that LBX2-AS1 knockdown suppressed ESCC cell migration and epithelial-mesenchymal transition (EMT). Zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) are two EMT-related transcription factors. Since LBX2-AS1 promoted the EMT progress and simultaneously enhanced the level of ZEB1 and ZEB2, we further investigated whether LBX2-AS1 promoted cell migration and EMT in ESCC by regulating ZEB1 and ZEB2. Mechanism investigations revealed that RNA binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) could interact with LBX2-AS1, ZEB1 and ZEB2, simultaneously. The similar function of HNRNPC in regulating migration and EMT process was demonstrated. ZEBI has been reported as a positive transcriptional regulator of lncRNA. Therefore, further mechanism analysis was made to demonstrate whether ZEB1 could regulate the transcription of LBX2-AS1. Collectively, our data showed that ZEB1-induced upregulation of LBX2-AS1 promoted cell migration and EMT process in ESCC via enhancing the stability of ZEB1 and ZEB2. (C) 2019 Elsevier Inc. All rights reserved.
引用
收藏
页码:566 / 572
页数:7
相关论文
共 32 条
[1]   miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy [J].
Adam, Liana ;
Zhong, Meng ;
Choi, Woonyoung ;
Qi, Wei ;
Nicoloso, Milena ;
Arora, Ameeta ;
Calin, George ;
Wang, Hua ;
Siefker-Radtke, Arlene ;
McConkey, David ;
Bar-Eli, Menashe ;
Dinney, Colin .
CLINICAL CANCER RESEARCH, 2009, 15 (16) :5060-5072
[2]   The Long Intergenic Noncoding RNA UFC1, a Target of MicroRNA 34a, Interacts With the mRNA Stabilizing Protein HuR to Increase Levels of β-Catenin in HCC Cells [J].
Cao, Chuanhui ;
Sun, Jingyuan ;
Zhang, Dongyan ;
Guo, Xuejun ;
Xie, Liwei ;
Li, Xin ;
Wu, Dehua ;
Liu, Li .
GASTROENTEROLOGY, 2015, 148 (02) :415-U249
[3]   Overexpression of lncRNA HOXA11-AS promotes cell epithelial-mesenchymal transition by repressing miR-200b in non-small cell lung cancer [J].
Chen, Jian-Hui ;
Zhou, Li-Yang ;
Xu, Suo ;
Zheng, Yu-Long ;
Wan, Yu-Feng ;
Hu, Cheng-Ping .
CANCER CELL INTERNATIONAL, 2017, 17
[4]   Long noncoding RNAs in mammalian cells: what, where, and why? [J].
Chen, Ling-Ling ;
Carmichael, Gordon G. .
WILEY INTERDISCIPLINARY REVIEWS-RNA, 2010, 1 (01) :2-21
[5]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[6]   Upregulation of long noncoding RNA HOTTIP promotes metastasis of esophageal squamous cell carcinoma via induction of EMT [J].
Chen, Xuemei ;
Han, Hongyu ;
Li, Yuqi ;
Zhang, Qiongxia ;
Mo, Kailan ;
Chen, Size .
ONCOTARGET, 2016, 7 (51) :84480-84485
[7]   The functional role of long non-coding RNA in human carcinomas [J].
Gibb, Ewan A. ;
Brown, Carolyn J. ;
Lam, Wan L. .
MOLECULAR CANCER, 2011, 10
[8]   Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205 [J].
Hirata, Hiroshi ;
Hinoda, Yuji ;
Shahryari, Varahram ;
Deng, Guoren ;
Nakajima, Koichi ;
Tabatabai, Z. Laura ;
Ishii, Nobuhisa ;
Dahiya, Rajvir .
CANCER RESEARCH, 2015, 75 (07) :1322-1331
[9]   Long noncoding RNA OCC-1 suppresses cell growth through destabilizing HuR protein in colorectal cancer [J].
Lan, Yang ;
Xiao, Xuewei ;
He, Zhengchi ;
Luo, Yu ;
Wu, Chuanfang ;
Li, Ling ;
Song, Xu .
NUCLEIC ACIDS RESEARCH, 2018, 46 (11) :5809-5821
[10]   Azithromycin decreases NALP3 mRNA stability in monocytes to limit inflammasome-dependent inflammation [J].
Lendermon, Elizabeth A. ;
Coon, Tiffany A. ;
Bednash, Joseph S. ;
Weathington, Nathaniel M. ;
McDyer, John F. ;
Mallampalli, Rama K. .
RESPIRATORY RESEARCH, 2017, 18