miR‑512‑5p suppresses the progression of non‑small cell lung cancer by targeting β‑catenin

Wang,Zhexin; Zhu,Xiaolei; Zhang,Tuo; Yao,Feng

doi:10.3892/ol.2019.11102

miR‑512‑5p suppresses the progression of non‑small cell lung cancer by targeting β‑catenin

Authors:
- Zhexin Wang
- Xiaolei Zhu
- Tuo Zhang
- Feng Yao
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Affiliations: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Suzhou Institute of Systems Medicine, Centre of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu 223300, P.R. China
Published online on: November 14, 2019 https://doi.org/10.3892/ol.2019.11102
Pages: 415-423
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The oncogenic protein β‑catenin is regulated by microRNAs (miRs) in non‑small cell lung cancer (NSCLC). miR‑512‑5p is downregulated in NSCLC compared with healthy tissues and exhibits a tumour‑suppressive effect. To study whether miR‑512‑5p acts on β‑catenin to exert its anticancer effect in NSCLC, miR‑512‑5p mimic and inhibitor were transfected into NSCLC A549 and H1975 cells. miR‑512‑5p mimic inhibited the invasion of NSCLC cells and increased apoptosis, which suggested an inhibitory effect of miR‑512‑5p in NSCLC progression in vitro. By contrast, transfection with the miR‑512‑5p inhibitor resulted in the opposite effects. A dual‑luciferase assay demonstrated that miR‑512‑5p complementarily bound to the 3'‑untranslated region of β‑catenin. miR‑512‑5p mimic suppressed the transcription and translation of β‑catenin and reduced the expression of the downstream oncogenes cyclin D1 and matrix metalloproteinases, leading to the inhibition of Wnt/β‑catenin signalling and subsequent inhibition of NSCLC tumourigenesis in vitro. In conclusion, miR‑512‑5p may function as a tumour suppressor in NSCLC by inhibiting the Wnt/β‑catenin pathway.

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1	Zhang H, Liu C, Tan Z and Zhang T: Segmentectomy versus Wedge resection for stage I non-small cell lung cancer: A Meta-analysis. J Surg Res. 243:371–379. 2019. View Article : Google Scholar : PubMed/NCBI
2	Liu H, Yin Q, Yang G and Qie P: Including 3564 patients prognostic impact of tumor spread through air spaces in non-small cell lung cancers: A meta-analysis. Pathol Oncol Res. 2019.(Epub ahead of print).
3	Im Y, Park HY, Shin S, Shin SH, Lee H, Ahn JH, Sohn I, Cho JH, Kim HK, Zo JI, et al: Prevalence of and risk factors for pulmonary complications after curative resection in otherwise healthy elderly patients with early stage lung cancer. Respir Res. 20:1362019. View Article : Google Scholar : PubMed/NCBI
4	Hung JJ, Jeng WJ, Hsu WH, Chou TY, Huang BS and Wu YC: Predictors of death, local recurrence, and distant metastasis in completely resected pathological stage-I non-small-cell lung cancer. J Thorac Oncol. 7:1115–1123. 2012. View Article : Google Scholar : PubMed/NCBI
5	Peng B, Zhang J, Woods JS and Peng W: Molecular markers and pathogenically targeted therapy in non-small cell lung cancer. Front Med China. 3:245–255. 2009. View Article : Google Scholar
6	Stewart DJ: Wnt signaling pathway in non-small cell lung cancer. J Natl Cancer Inst. 106:djt3562014. View Article : Google Scholar : PubMed/NCBI
7	Shang S, Hua F and Hu ZW: The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget. 8:33972–33989. 2017. View Article : Google Scholar : PubMed/NCBI
8	Xu X, Sun PL, Li JZ, Jheon S, Lee CT and Chung JH: Aberrant Wnt1/β-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery. J Thorac Oncol. 6:716–724. 2011. View Article : Google Scholar : PubMed/NCBI
9	Paul S and Dey A: Wnt signaling and cancer development: Therapeutic implication. Neoplasma. 55:165–176. 2008.PubMed/NCBI
10	Chen W, Huang Y, Zhang S, Zheng X, Xie S, Mao J, Cai Y, Lu X, Hu L, Shen J, et al: MicroRNA-212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin-specific protease-9. J Cell Biochem. 120:6482–6489. 2019. View Article : Google Scholar : PubMed/NCBI
11	Jiang C, Bi C, Jiang X, Tian T, Huang X, Wang C, Fernandez MR, Iqbal J, Chan WC, McKeithan TW, et al: The miR-17~92 cluster activates mTORC1 in mantle cell lymphoma by targeting multiple regulators in the STK11/AMPK/TSC/mTOR pathway. Br J Haematol. 185:616–620. 2019. View Article : Google Scholar : PubMed/NCBI
12	Li JP, Liao XH, Xiang Y, Yao A, Song RH, Zhang ZJ, Huang F, Dai ZT and Zhang TC: Hyperoside and let-7a-5p synergistically inhibits lung cancer cell proliferation via inducing G1/S phase arrest. Gene. 679:232–240. 2018. View Article : Google Scholar : PubMed/NCBI
13	Loo JM, Scherl A, Nguyen A, Man FY, Weinberg E, Zeng Z, Saltz L, Paty PB and Tavazoie SF: Extracellular metabolic energetics can promote cancer progression. Cell. 160:393–406. 2015. View Article : Google Scholar : PubMed/NCBI
14	John K, Wu J, Lee BW and Farah CS: MicroRNAs in head and neck cancer. Int J Dent. 2013:6502182013. View Article : Google Scholar : PubMed/NCBI
15	Dinami R, Buemi V, Sestito R, Zappone A, Ciani Y, Mano M, Petti E, Sacconi A, Blandino G, Giacca M, et al: Epigenetic silencing of miR-296 and miR-512 ensures hTERT dependent apoptosis protection and telomere maintenance in basal-type breast cancer cells. Oncotarget. 8:95674–95691. 2017. View Article : Google Scholar : PubMed/NCBI
16	Chu K, Gao G, Yang X, Ren S, Li Y, Wu H, Huang Y and Zhou C: miR-512-5p induces apoptosis and inhibits glycolysis by targeting p21 in non-small cell lung cancer cells. Int J Oncol. 48:577–586. 2016. View Article : Google Scholar : PubMed/NCBI
17	Li J, Lei H, Xu Y and Tao ZZ: miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo. PLoS One. 10:e01352652015. View Article : Google Scholar : PubMed/NCBI
18	Niu X, Liu S, Jia L and Chen J: Role of miR-3619-5p in β-catenin-mediated non-small cell lung cancer growth and invasion. Cell Physiol Biochem. 37:1527–1536. 2015. View Article : Google Scholar : PubMed/NCBI
19	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
20	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
21	Xu H, Lin D, Wang L, Liu N and Wang E: Expression and mutation of β-catenin in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 7:409–413. 2004.(In Chinese). PubMed/NCBI
22	Vargas DA, Sun M, Sadykov K, Kukuruzinska MA and Zaman MH: The integrated role of Wnt/β-catenin, N-glycosylation, and E-cadherin-mediated adhesion in network dynamics. PLoS Comput Biol. 12:e10050072016. View Article : Google Scholar : PubMed/NCBI
23	Xie C, Jiang G, Fan C, Zhang X, Zhang Y, Miao Y, Lin X, Wu J, Wang L, Liu Y, et al: ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway. Tumour Biol. 35:8903–8911. 2014. View Article : Google Scholar : PubMed/NCBI
24	Schneikert J and Behrens J: The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut. 56:417–425. 2007. View Article : Google Scholar : PubMed/NCBI
25	Shu Z, Chen L and Ding D: miR-582-5P induces colorectal cancer cell proliferation by targeting adenomatous polyposis coli. World J Surg Oncol. 14:2392016. View Article : Google Scholar : PubMed/NCBI
26	Li M, Tian L, Wang L, Yao H, Zhang J, Lu J, Sun Y, Gao X, Xiao H and Liu M: Down-regulation of miR-129-5p inhibits growth and induces apoptosis in laryngeal squamous cell carcinoma by targeting APC. PLoS One. 8:e778292013. View Article : Google Scholar : PubMed/NCBI
27	Wang S, Dong Y, Zhang Y, Wang X, Xu L, Yang S, Li X, Dong H, Xu L, Su L, et al: DACT2 is a functional tumor suppressor through inhibiting Wnt/β-catenin pathway and associated with poor survival in colon cancer. Oncogene. 34:2575–2585. 2015. View Article : Google Scholar : PubMed/NCBI
28	Yang Y, Yang JJ, Tao H and Jin WS: New perspectives on β-catenin control of cell fate and proliferation in colon cancer. Food Chem Toxicol. 740:14–19. 2014. View Article : Google Scholar