Long non-coding RNA ZEB1-AS1 promotes cell invasion and epithelial to mesenchymal transition through inducing ZEB1 expression in cervical cancer

被引:32
作者
Cheng, Rongjie [1 ]
Li, Nan [2 ]
Yang, Shuyan [1 ]
Liu, Lei [1 ]
Han, Shiyu [1 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 4, Dept Obstet & Gynaecol, 37 Yiyuan Rd, Harbin 150001, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Affiliated Hosp 4, Dept Pathol, Harbin, Heilongjiang, Peoples R China
关键词
cervical cancer; long non-coding RNA; ZEB1-AS1; epithelial-mesenchymal transition; ZEB1; POOR-PROGNOSIS; PROGRESSION; METASTASIS;
D O I
10.2147/OTT.S179937
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Long non-coding RNAs (lncRNAs) play important roles in cancer initiation and development. The purpose of the present study was to determine the functions and mechanisms of lncRNA ZEB1-AS1 in human cervical cancer (CC). Methods: A total of 106 pairs of CC tissues and adjacent normal epithelial tissues were collected from CC patients who underwent resection. Three human CC cell lines (HeLa, C33A and SiHa) and a normal cervical cell line Crl-2614 and were transfected with human ZEB1-AS1 cDNA, or empty vector as the control. Then, cells were transfected with ZEB1-AS1-specific small interfering RNA (si-ZEB1-AS1), ZEB1-specific siRNA (si-ZEB1) or negative siRNA control (si-NC). The transfection efficiency was confirmed by RT-qPCR analysis. qPCR was applied to determine the qualification of RNA. Cell proliferation was investigated by MTT assay. The apoptosis rate of cells was detected by flow cytometer. Cell invasion was detected by transwell assay. Western blot was applied to determine the expression of proteins. CC xenografts in 12 male BALB/c athymic nude mice were established. And the tumor volumes were measured by vernier caliper. Results: We found that ZEB1-AS1 expression was remarkably increased in human CC tissue samples and cell lines, and its expression levels were closely associated with poor prognosis of CC patients. Moreover, we found that knockdown of ZEB1-AS1 inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of CC cells in vitro and suppressed CC xenograft tumor growth in vivo. Mechanistically, we found that knockdown of ZEB1-AS1 significantly inhibited ZEB1 expression, and knockdown of ZEB1 could rescue the effects of ZEB1-AS1 overexpression in CC cells. Conclusion: In conclusion, our findings indicated that ZEB1-AS1 serves an oncogenic role in CC, which might become a potential prognostic indicator and therapeutic target in CC.
引用
收藏
页码:7245 / 7253
页数:9
相关论文
共 20 条
[1]   Treatment of metastatic cervical cancer: Future directions involving targeted agents [J].
Diaz-Padilla, Ivan ;
Monk, Bradley J. ;
Mackay, Helen J. ;
Oaknin, Ana .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2013, 85 (03) :303-314
[2]   Long noncoding RNA ZEB1-AS1 expression predicts progression and poor prognosis of colorectal cancer [J].
Fu, Jining ;
Cui, Yongyuan .
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, 2017, 32 (04) :E428-E433
[3]   The emerging role of IncRNAs in cancer [J].
Huarte, Maite .
NATURE MEDICINE, 2015, 21 (11) :1253-1261
[4]  
JEMAL A, 2011, CA-CANCER J CLIN, V61, P134, DOI [DOI 10.3322/caac.20115, DOI 10.3322/CAAC.20107]
[5]   ZEB1-AS1: A crucial cancer-related long non-coding RNA [J].
Li, Jinglin ;
Li, Zhenglong ;
Leng, Kaiming ;
Xu, Yi ;
Ji, Daolin ;
Huang, Lining ;
Cui, Yunfu ;
Jiang, Xingming .
CELL PROLIFERATION, 2018, 51 (01)
[6]   RETRACTED: Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma (Retracted article. See vol. 41, pg. 4839, 2022) [J].
Li, T. ;
Xie, J. ;
Shen, C. ;
Cheng, D. ;
Shi, Y. ;
Wu, Z. ;
Deng, X. ;
Chen, H. ;
Shen, B. ;
Peng, C. ;
Li, H. ;
Zhan, Q. ;
Zhu, Z. .
ONCOGENE, 2016, 35 (12) :1575-1584
[7]   LncRNA ZEB1-AS1 predicts unfavorable prognosis in gastric cancer [J].
Li, Yanliang ;
Wen, Xiaowen ;
Wang, Longgang ;
Sun, Xianjun ;
Ma, Heng ;
Fu, Zheng ;
Li, Leping .
SURGICAL ONCOLOGY-OXFORD, 2017, 26 (04) :527-534
[8]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[9]   A Long Noncoding RNA ZEB1-AS1 Promotes Tumorigenesis and Predicts Poor Prognosis in Glioma [J].
Lv, Qiao-Li ;
Hu, Lei ;
Chen, Shu-Hui ;
Sun, Bao ;
Fu, Meng-Long ;
Qin, Chong-Zhen ;
Qu, Qiang ;
Wang, Gui-Hua ;
He, Chen-Jie ;
Zhou, Hong-Hao .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (09)
[10]  
Ma TT, 2018, EUR REV MED PHARMACO, V22, P1907, DOI 10.26355/eurrev_201804_14713