MicroRNA-545 targets ZEB2 to inhibit the development of non‑small cell lung cancer by inactivating Wnt/β-catenin pathway

Cui,Jianying; Pan,Guodong; He,Qingjuan; Yin,Lizhi; Guo,Rui; Bi,Hongmei

doi:10.3892/ol.2019.10619

MicroRNA-545 targets ZEB2 to inhibit the development of non‑small cell lung cancer by inactivating Wnt/β-catenin pathway

Authors:
- Jianying Cui
- Guodong Pan
- Qingjuan He
- Lizhi Yin
- Rui Guo
- Hongmei Bi
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Affiliations: Department of Respiratory Medicine, Anqiu People's Hospital, Weifang, Shandong 262100, P.R. China, Department of Thoracic Surgery, Traditional Chinese Medical Hospital of Huangdao District, Qingdao, Shandong 266500, P.R. China, Department of Respiratory Medicine, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Health Management Center, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Outpatient Department, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Respiratory Medicine, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041, P.R. China
Published online on: July 15, 2019 https://doi.org/10.3892/ol.2019.10619
Pages: 2931-2938
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The specific function of microRNA-545 (miR-545) has been reported to regulate the development of human cancers. However, the effect of miR-545 is still unclear in non‑small cell lung cancer (NSCLC). Hence, this study explored the molecular mechanism of miR-545 in NSCLC. The expression levels of miR-545 and ZEB2 were measured through reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was detected by western blotting. Dual luciferase assay was applied to evaluate the relationship between miR-545 and zinc finger E-box‑binding homeobox 2 (ZEB2). MTT and Transwell assays were used to investigate the function of miR-545 in NSCLC. The expression of miR-545 was decreased in NSCLC tissues. The overexpression of miR-545 suppressed the migration, invasion and proliferation of NSCLC cells. Furthermore, ZEB2 was a direct target gene of miR-545. The knockout of ZEB2 suppressed the development of NSCLC. miR-545 inhibited the progression of NSCLC through targeting ZEB2. Moreover, miR-545 repressed the development of NSCLC via blocking EMT and Wnt/β-catenin pathway. In conclusion, miR-545 inhibited the progression of NSCLC through targeting ZEB2 and blocking EMT and Wnt/β-catenin pathway.

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1	Field JK, Oudkerk M, Pedersen JH and Duffy SW: Prospects for population screening and diagnosis of lung cancer. Lancet. 382:732–741. 2013. View Article : Google Scholar : PubMed/NCBI
2	Wang L, Yu C, Liu Y, Wang J, Li C, Wang Q, Wang P, Wu S and Zhang ZJ: Lung cancer mortality trends in China from 1988 to 2013: New challenges and opportunities for the government. Int J Environ Res Public Health. 13:E10522016. View Article : Google Scholar : PubMed/NCBI
3	Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM and Peters S; ESMO Guidelines Working Group, : Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 25 (Suppl 3):iii27–iii39. 2014. View Article : Google Scholar : PubMed/NCBI
4	Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI
5	Araujo LH and Carbone DP: Non-small cell lung cancer genomics around the globe: Focus on ethnicity. J Thorac Dis. 9:E392–E394. 2017. View Article : Google Scholar : PubMed/NCBI
6	Lv X, Li CY, Han P and Xu XY: MicroRNA-520a-3p inhibits cell growth and metastasis of non-small cell lung cancer through PI3K/AKT/mTOR signaling pathway. Eur Rev Med Pharmacol Sci. 22:2321–2327. 2018.PubMed/NCBI
7	Fei X, Zhang J, Zhao Y, Sun M, Zhao H and Li S: miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells. Oncol Lett. 15:9081–9086. 2018.PubMed/NCBI
8	Song B, Ji W, Guo S, Liu A, Jing W, Shao C, Li G and Jin G: miR-545 inhibited pancreatic ductal adenocarcinoma growth by targeting RIG-I. FEBS Lett. 588:4375–4381. 2014. View Article : Google Scholar : PubMed/NCBI
9	Cosín-Tomás M, Antonell A, Lladó A, Alcolea D, Fortea J, Ezquerra M, Lleó A, Martí MJ, Pallàs M, Sanchez-Valle R, et al: Plasma miR-34a-5p and miR-545-3p as early biomarkers of Alzheimer's disease: Potential and limitations. Mol Neurobiol. 54:5550–5562. 2017. View Article : Google Scholar : PubMed/NCBI
10	Du B, Wang Z, Zhang X, Feng S, Wang G, He J and Zhang B: MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells. PLoS One. 9:e880222014. View Article : Google Scholar : PubMed/NCBI
11	Gheldof A, Hulpiau P, van Roy F, De Craene B and Berx G: Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 69:2527–2541. 2012. View Article : Google Scholar : PubMed/NCBI
12	Chua HL, Bhat-Nakshatri P, Clare SE, Morimiya A, Badve S and Nakshatri H: NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2. Oncogene. 26:711–724. 2007. View Article : Google Scholar : PubMed/NCBI
13	You J, Li Y, Fang N, Liu B, Zu L, Chang R, Li X and Zhou Q: MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2. PLoS One. 9:e918272014. View Article : Google Scholar : PubMed/NCBI
14	Cong N, Du P, Zhang A, Shen F, Su J, Pu P, Wang T, Zjang J, Kang C and Zhang Q: Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncol Rep. 29:1579–1587. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhang Q, Zhang B, Sun L, Yan Q, Zhang Y, Zhang Z, Su Y and Wang C: MicroRNA-130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β-catenin pathway. Cell Biochem Funct. 36:194–202. 2018. View Article : Google Scholar : PubMed/NCBI
16	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 : PubMed/NCBI
17	Brown BD and Naldini L: Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet. 10:578–585. 2009. View Article : Google Scholar : PubMed/NCBI
18	Han L, Chen W, Xia Y, Song Y, Zhao Z, Cheng H and Jiang T: MiR-101 inhibits the proliferation and metastasis of lung cancer by targeting zinc finger E-box binding homeobox 1. Am J Transl Res. 10:1172–1183. 2018.PubMed/NCBI
19	Zhang W, Qiao B and Fan J: Overexpression of miR-4443 promotes the resistance of non-small cell lung cancer cells to epirubicin by targeting INPP4A and regulating the activation of JAK2/STAT3 pathway. Pharmazie. 73:386–392. 2018.PubMed/NCBI
20	Liao C, Xiao W, Zhu N, Liu Z, Yang J, Wang Y and Hong M: MicroR-545 enhanced radiosensitivity via suppressing Ku70 expression in Lewis lung carcinoma xenograft model. Cancer Cell Int. 15:562015. View Article : Google Scholar : PubMed/NCBI
21	Liu Z, Dou C, Yao B, Xu M, Ding L, Wang Y, Jia Y, Li Q, Zhang H, Tu K, et al: Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma. Oncotarget. 7:25350–25365. 2016.PubMed/NCBI
22	Jia X, Liu X, Li M, Zeng Y, Feng Z, Su X, Huang Y, Chen M and Yang X: Potential tumor suppressing role of microRNA-545 in epithelial ovarian cancer. Oncol Lett. 15:6386–6392. 2018.PubMed/NCBI
23	Huang X and Lu S: MicroR-545 mediates colorectal cancer cells proliferation through up-regulating epidermal growth factor receptor expression in HOTAIR long non-coding RNA dependent. Mol Cell Biochem. 431:45–54. 2017. View Article : Google Scholar : PubMed/NCBI
24	Lin X, Yang Z, Zhang P, Liu Y and Shao G: miR-154 inhibits migration and invasion of human non-small cell lung cancer by targeting ZEB2. Oncol Lett. 12:301–306. 2016. View Article : Google Scholar : PubMed/NCBI
25	Fei D, Zhao K, Yuan H, Xing J and Zhao D: MicroRNA-187 exerts tumor-suppressing functions in osteosarcoma by targeting ZEB2. Am J Cancer Res. 6:2859–2868. 2016.PubMed/NCBI
26	Jiao A, Sui M, Zhang L, Sun P, Geng D, Zhang W, Wang X and Li J: MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator. Mol Med Rep. 13:3349–3355. 2016. View Article : Google Scholar : PubMed/NCBI
27	Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D and van Roy F: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 7:1267–1278. 2001. View Article : Google Scholar : PubMed/NCBI
28	Shi ZM, Wang L, Shen H, Jiang CF, Ge X, Li DM, Wen YY, Sun HR, Pan MH, Li W, et al: Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling. Oncogene. 36:2577–2588. 2017. View Article : Google Scholar : PubMed/NCBI
29	Qi S, Song Y, Peng Y, Wang H, Long H, Yu X, Li Z, Fang L, Wu A, Luo W, et al: ZEB2 mediates multiple pathways regulating cell proliferation, migration, invasion, and apoptosis in glioma. PLoS One. 7:e388422012. View Article : Google Scholar : PubMed/NCBI
30	Polakis P: Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 4:a0080522012. View Article : Google Scholar : PubMed/NCBI
31	Wang XH, Cui YX, Wang ZM and Liu J: Down-regulation of FOXR2 inhibits non-small cell lung cancer cell proliferation and invasion through the Wnt/β-catenin signaling pathway. Biochem Biophys Res Commun. 500:229–235. 2018. View Article : Google Scholar : PubMed/NCBI
32	Zhou DD, Wang X, Wang Y, Xiang XJ, Liang ZC, Zhou Y, Xu A, Bi CH and Zhang L: MicroRNA-145 inhibits hepatic stellate cell activation and proliferation by targeting ZEB2 through Wnt/β-catenin pathway. Mol Immunol. 75:151–160. 2016. View Article : Google Scholar : PubMed/NCBI