ZEB2-AS1 Accelerates Epithelial/Mesenchymal Transition Through miR-1205/CRKL Pathway in Colorectal Cancer

被引:20
作者
Jiang, Yinghao [1 ]
Liu, Guangming [2 ]
Ye, Wei [1 ]
Xie, Jianjin [1 ]
Shao, Chunfa [1 ]
Wang, Xiaowei [1 ]
Li, Xia [1 ]
机构
[1] First Peoples Hosp Wenling, Dept Anorectal Surg, Wenling, Peoples R China
[2] First Hosp Jilin Univ, Dept Gastroenterol, Changchun, Peoples R China
关键词
colorectal cancer; CRKL; epithelial; mesenchymal transition; miR-1205; ZEB2-AS1; EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR SNAIL; E-CADHERIN; METASTASIS; EXPRESSION; EMT; PROLIFERATION; REPRESSOR; CRKL;
D O I
10.1089/cbr.2019.3000
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Accumulating reports have demonstrated that long-noncoding RNAs (lncRNAs) play critical roles in the pathological progression of colorectal cancer (CRC). However, the role of lncRNA zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in CRC remains largely unknown. Methods: The authors detected the ZEB2-AS1 expression in CRC tissue sample and CRC cell lines. The effects of ZEB2-AS1 on CRC were identified through in vitro assays (i.e., transwell assay, wound-healing assay, immunofluorescence assay, and Western blot) in a ZEB2-AS1 knockdown system. The molecular mechanism of ZEB2-AS1 was explored via bioinformatic tools, quantitative real-time polymerase chain reaction (qRT-PCR), dual-luciferase reporter assay, RNA immunoprecipitation assay, and so on. Moreover, a series of gain-of-function experiments were performed to identify the effect of ZEB2-AS1 and miR-1205 on epithelial-to-mesenchymal transition (EMT) in CRC cells. Results: This analysis clarified that ZEB2-AS1 was upregulated in both CRC tissue sample and cells lines; meanwhile, the high expression of ZEB2-AS1 was correlated with poor overall survival rate. ZEB2-AS1 knockdown significantly suppresses the EMT in CRC cells. Furthermore, the authors identified that the expression of ZEB2-AS1 was negatively correlated with expression of miR-1205, and CRKL could be a direct target of miR-1205. Through the gain-of-function experiments, they found that ZEB2-AS1 accelerates EMT in CRC cells via modulating the expression of miR-1205 and CRKL. Conclusion: Taken together, this study revealed that ZEB2-AS1 accelerates EMT in CRC through the miR-1205/CRKL pathway, suggesting that ZEB2-AS1 may potentially serve as a target of CRC.
引用
收藏
页码:153 / 162
页数:10
相关论文
共 39 条
[21]   Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells [J].
Li, Yuan ;
Huang, Shengkai ;
Li, Yan ;
Zhang, Weilong ;
He, Kun ;
Zhao, Mei ;
Lin, Hong ;
Li, Dongdong ;
Zhang, Honggang ;
Zheng, Zhaoxu ;
Huang, Changzhi .
TUMOR BIOLOGY, 2016, 37 (10) :14205-14215
[22]   The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer [J].
Liang, Wei-Cheng ;
Fu, Wei-Ming ;
Wong, Cheuk-Wa ;
Wang, Yan ;
Wang, Wei-Mao ;
Hu, Guo-Xin ;
Zhang, Li ;
Xiao, Li-Jia ;
Wan, David Chi-Cheong ;
Zhang, Jin-Fang ;
Waye, Mary Miu-Yee .
ONCOTARGET, 2015, 6 (26) :22513-22525
[23]   LncRNA HIF1A-AS2 positively affects the progression and EMT formation of colorectal cancer through regulating miR-129-5p and DNMT3A [J].
Lin, Jinguan ;
Shi, Zhaohui ;
Yu, Zhiyuan ;
He, Zhe .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 98 :433-439
[24]   Epidemiology and management of liver metastases from colorectal cancer [J].
Manfredi, Sylvain ;
Lepage, Come ;
Hatem, Cyril ;
Coatmeur, Olivier ;
Faivre, Jean ;
Bouvier, Anne-Marie .
ANNALS OF SURGERY, 2006, 244 (02) :254-259
[25]   The Current Role of Robotics in Colorectal Surgery [J].
Mushtaq H.H. ;
Shah S.K. ;
Agarwal A.K. .
Current Gastroenterology Reports, 2019, 21 (3)
[26]   Organization of the mouse Zjhx1b gene encoding the two-handed zinc finger repressor Smad-interacting protein-1 [J].
Nelles, L ;
Van de Putte, T ;
van Grunsven, L ;
Huylebroeck, D ;
Verschueren, K .
GENOMICS, 2003, 82 (04) :460-469
[27]  
POULTER CA, 1992, CANCER, V70, P1434, DOI 10.1002/1097-0142(19920901)70:3+<1434::AID-CNCR2820701535>3.0.CO
[28]  
2-A
[29]   Noncoding RNAs as novel biomarkers in pancreatic cancer: what do we know? [J].
Previdi, Maria C. ;
Carotenuto, Pietro ;
Zito, Domenico ;
Pandolfo, Rosantony ;
Braconi, Chiara .
FUTURE ONCOLOGY, 2017, 13 (05) :443-453
[30]   Stage IV colorectal cancer primary site and patterns of distant metastasis [J].
Robinson, Jamaica R. ;
Newcomb, Polly A. ;
Hardikar, Sheetal ;
Cohen, Stacey A. ;
Phipps, Amanda I. .
CANCER EPIDEMIOLOGY, 2017, 48 :92-95