lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1

Zhao,Xin; Wang,Dongwen; Ding,Yongxue; Zhou,Jingmin; Liu,Guanghua; Ji,Zhigang

doi:10.3892/ijmm.2019.4187

lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1

Authors:
- Xin Zhao
- Dongwen Wang
- Yongxue Ding
- Jingmin Zhou
- Guanghua Liu
- Zhigang Ji
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Affiliations: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Urology, Liaoyang City Central Hospital, Liaoyang, Liaoning 111000, P.R. China
Published online on: May 8, 2019 https://doi.org/10.3892/ijmm.2019.4187
Pages: 196-206
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The prognosis for patients with metastatic bladder cancer (BCa) is poor, and has not been improved by current treatment methods. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of zinc finger E‑box‑binding homeobox 1‑antisense 1 (ZEB1‑AS1) in BCa progression and metastasis remains unclear. The present study determined the expression level of ZEB1‑AS1 in BCa and additionally investigated the functional role of ZEB1‑AS1 in BCa metastasis. Reverse transcription quantitative polymerase chain reaction analysis showed that ZEB1‑AS1 was upregulated in BCa cells compared with normal epithelial cells. Functionally, knockdown of ZEB1‑AS1 suppressed BCa cell migration and invasion in vitro, and metastasis in vivo. Mechanistic investigations revealed that ZEB1‑AS1 bound to heterogenous nuclear ribonucleoprotein D0 (AUF1), thereby activating the translation of ZEB1 mRNA without affecting its mRNA level. In addition, ZEB1‑AS1 was significantly upregulated in BCa tissues and muscle‑invasive BCa cases. ROC curve analysis demonstrated that ZEB1‑AS1 expression was associated with metastasis in patients with BCa. In conclusion, the data from the present study demonstrated that ZEB1‑AS1 induced BCa metastasis via an AUF1‑mediated translation activation of ZEB1 mRNA mechanism. ZEB1‑AS1 may serve as a promising target for clinical intervention in advanced BCa.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
3	Van Batavia J, Yamany T, Molotkov A, Dan H, Mansukhani M, Batourina E, Schneider K, Oyon D, Dunlop M, Wu XR, et al: Bladder cancers arise from distinct urothelial sub-populations. Nat Cell Biol. 16:982–991. 1–5. 2014. View Article : Google Scholar : PubMed/NCBI
4	Youssef RF and Raj GV: Lymphadenectomy in management of invasive bladder cancer. Int J Surg Oncol. 2011:7581892011.
5	Wu XR: Urothelial tumorigenesis: A tale of divergent pathways. Nat Rev Cancer. 5:713–725. 2005. View Article : Google Scholar : PubMed/NCBI
6	Hautmann RE, de Petriconi RC, Pfeiffer C and Volkmer BG: Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: Long-term results in 1,100 patients. Eur Urol. 61:1039–1047. 2012. View Article : Google Scholar : PubMed/NCBI
7	Cao Y: Opinion: Emerging mechanisms of tumour lymphan-giogenesis and lymphatic metastasis. Nat Rev Cancer. 5:735–743. 2005. View Article : Google Scholar : PubMed/NCBI
8	Karaman S and Detmar M: Mechanisms of lymphatic metastasis. J Clin Invest. 124:922–928. 2014. View Article : Google Scholar : PubMed/NCBI
9	Loewen G, Jayawickramarajah J, Zhuo Y and Shan B: Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 7:902014. View Article : Google Scholar : PubMed/NCBI
10	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar
11	Nakagawa S and Kageyama Y: Nuclear lncRNAs as epigenetic regulators-beyond skepticism. Biochim Biophys Acta. 1839:215–222. 2014. View Article : Google Scholar
12	Kornienko AE, Guenzl PM, Barlow DP and Pauler FM: Gene regulation by the act of long non-coding RNA transcription. BMC Biol. 11:592013. View Article : Google Scholar : PubMed/NCBI
13	Ni W, Zhang Y, Zhan Z, Ye F, Liang Y, Huang J, Chen K, Chen L and Ding Y: A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquiti-nation of LATS1. J Hematol Oncol. 10:912017. View Article : Google Scholar
14	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
15	Chen DL, Lu YX, Zhang JX, Wei XL, Wang F, Zeng ZL, Pan ZZ, Yuan YF, Wang FH, Pelicano H, et al: Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression. Theranostics. 7:4836–4849. 2017. View Article : Google Scholar : PubMed/NCBI
16	Liu G, Ye Z, Zhao X and Ji Z: SP1-induced up-regulation of lncRNA SNHG14 as a ceRNA promotes migration and invasion of clear cell renal cell carcinoma by regulating N-WASP. Am J Cancer Res. 7:2515–2525. 2017.
17	Lin J, Zhan Y, Liu Y, Chen Z, Liang J, Li W, He A, Zhou L, Mei H, Wang F and Huang W: Increased expression of ZEB1-AS1 correlates with higher histopathological grade and promotes tumorigenesis in bladder cancer. Oncotarget. 8:24202–24212. 2017.PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). method Methods. 25:402–408. 2001. View Article : Google Scholar
19	Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL and Massagué J: Genes that mediate breast cancer metastasis to lung. Nature. 436:518–524. 2005. View Article : Google Scholar : PubMed/NCBI
20	Chen X, Gu P, Xie R, Han J, Liu H, Wang B, Xie W, Xie W, Zhong G, Chen C, et al: Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer. J Cell Mol Med. 21:1266–1279. 2017. View Article : Google Scholar :
21	Gong X, Du X, Xu Y and Zheng W: LINC00037 inhibits proliferation of renal cell carcinoma cells in an epidermal growth factor receptor-dependent way. Cell Physiol Biochem. 45:523–536. 2018. View Article : Google Scholar : PubMed/NCBI
22	Lu QC, Rui ZH, Guo ZL, Xie W, Shan S and Ren T: LncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression. J Cell Mol Med. 22:1527–1537. 2018. View Article : Google Scholar
23	Moore AE, Chenette DM, Larkin LC and Schneider RJ: Physiological networks and disease functions of RNA-binding protein AUF1. Wiley Interdiscip Rev RNA. 5:549–564. 2014. View Article : Google Scholar : PubMed/NCBI
24	Ulitsky I and Bartel DP: lincRNAs: Genomics, evolution, and mechanisms. Cell. 154:26–46. 2013. View Article : Google Scholar : PubMed/NCBI
25	Xu TP, Wang YF, Xiong WL, Ma P, Wang WY, Chen WM, Huang MD, Xia R, Wang R, Zhang EB, et al: E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis. Cell Death Dis. 8:e28372017. View Article : Google Scholar : PubMed/NCBI
26	Su W, Xu M, Chen X, Chen N, Gong J, Nie L, Li L, Li X, Zhang M and Zhou Q: Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer. Mol Cancer. 16:1422017. View Article : Google Scholar : PubMed/NCBI
27	Xiong WC, Han N, Wu N, Zhao KL, Han C, Wang HX, Ping GF, Zheng PF, Feng H, Qin L and He P: Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells. Am J Transl Res. 10:605–617. 2018.PubMed/NCBI
28	Lv QL, Hu L, Chen SH, Sun B, Fu ML, Qin CZ, Qu Q, Wang GH, He CJ and Zhou HH: A long noncoding RNA ZEB1-AS1 promotes tumorigenesis and predicts poor prognosis in glioma. Int J Mol Sci. 17:E14312016. View Article : Google Scholar : PubMed/NCBI
29	Cheng R, Li N, Yang S, Liu L and Han S: Long non-coding RNA ZEB1-AS1 promotes cell invasion and epithelial to mesenchymal transition through inducing ZEB1 expression in cervical cancer. Onco Targets Ther. 11:7245–7253. 2018. View Article : Google Scholar : PubMed/NCBI
30	Liu C and Lin J: Long noncoding RNA-ZEB1 AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1. Am J Transl Res. 8:4095–4105. 2016.
31	Qu R, Chen X and Zhang C: LncRNA ZEB1-AS1/miR-409-3p/ZEB1 feedback loop is involved in the progression of non-small cell lung cancer. Biochem Biophys Res Commun. 507:450–456. 2018. View Article : Google Scholar : PubMed/NCBI
32	Choi YJ, Yoon JH and Chang JH: Crystal structure of the N-Terminal RNA recognition motif of mRNA decay regulator AUF1. Biomed Res Int. 2016:32861912016. View Article : Google Scholar : PubMed/NCBI
33	Li S, Zhang HY, Du ZX, Li C, An MX, Zong ZH, Liu BQ and Wang HQ: Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells. Oncotarget. 7:70364–70377. 2016.PubMed/NCBI