Abstract
MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth; however, whether miR-429 may also regulate the invasion of GC cells is unknown. Here, we showed that miR-429 levels were significantly decreased and ZEB1 and ZEB2 levels were significantly increased in GC specimens, compared to the paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-429 and ZEB1 or ZEB2 inversely correlated in GC specimens. Bioinformatics analyses showed that miR-429 targeted the 3′-untranslated region of both ZEB1 and ZEB2 mRNA to inhibit their translation, which was confirmed by luciferase reporter assay. Overexpression of miR-429 inhibited ZEB1/2-mediated cell invasiveness, while depletion of miR-429 augmented it. Together, our data suggest that miR-429 suppression in GC promotes ZEB1/2-mediated cancer cell invasion.
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References
Zhao X, Li X, Yuan H. MicroRNAs in gastric cancer invasion and metastasis. Front Biosci. 2013;18:803–10.
Liu G, Jiang C, Li D, Wang R, Wang W. MiRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour Biol. 2014;35:9801–6.
Mao D, Zhang Y, Lu H, Zhang H. Molecular basis underlying inhibition of metastasis of gastric cancer by anti-VEGFa treatment. Tumour Biol. 2014;35:8217–23.
Ye Y, Zhou X, Li X, Tang Y, Sun Y, Fang J. Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of MMP7 and MMP13. Tumour Biol. 2014;35:10891–6.
Wu W, Ding H, Cao J, Zhang W. FBXL5 inhibits metastasis of gastric cancer through suppressing Snail1. Cell Physiol Biochem. 2015;35:1764–72.
Xu XY, Zhang LJ, Yu YQ, Zhang XT, Huang WJ, Nie XC, et al. Down-regulated MAC30 expression inhibits proliferation and mobility of human gastric cancer cells. Cell Physiol Biochem. 2014;33:1359–68.
Zhou X, Xia Y, Su J, Zhang G. Down-regulation of miR-141 induced by helicobacter pylori promotes the invasion of gastric cancer by targeting STAT4. Cell Physiol Biochem. 2014;33:1003–12.
Cui Y, Chen J, He Z, Xiao Y. SUZ12 depletion suppresses the proliferation of gastric cancer cells. Cell Physiol Biochem. 2013;31:778–84.
Di Leva G, Croce CM. MiRNA profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.
Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 2013;18:282–9.
Mei Q, Li F, Quan H, Liu Y, Xu H. Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo. Cancer Sci. 2014;105:755–62.
Wang F, Xiao W, Sun J, Han D, Zhu Y. MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma. Tumour Biol. 2014;35:8653–8.
Chen J, Wang L, Matyunina LV, Hill CG, McDonald JF. Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells. Gynecol Oncol. 2011;121:200–5.
Li J, Du L, Yang Y, Wang C, Liu H, Wang L, et al. MiR-429 is an independent prognostic factor in colorectal cancer and exerts its anti-apoptotic function by targeting SOX2. Cancer Lett. 2013;329:84–90.
Wang Y, Li M, Zang W, Ma Y, Wang N, Li P, et al. Mir-429 up-regulation induces apoptosis and suppresses invasion by targeting bcl-2 and sp-1 in esophageal carcinoma. Cell Oncol. 2013;36:385–94.
Cristobal I, Rincon R, Manso R, Carames C, Aguilera O, Madoz-Gurpide J, et al. Deregulation of miR-200b, miR-200c and miR-429 indicates its potential relevant role in patients with colorectal cancer liver metastasis. J Surg Oncol. 2014;110:484–5.
Gao H, Liu C. MiR-429 represses cell proliferation and induces apoptosis in HBV-related HCC. Biomed Pharmacother. 2014;68:943–9.
Liu X, Liu Y, Wu S, Shi X, Li L, Zhao J, et al. Tumor-suppressing effects of miR-429 on human osteosarcoma. Cell Biochem Biophys. 2014;70:215–24.
Sun Y, Shen S, Liu X, Tang H, Wang Z, Yu Z, et al. MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem. 2014;390:19–30.
Sun Y, Shen S, Tang H, Xiang J, Peng Y, Tang A, et al. MiR-429 identified by dynamic transcriptome analysis is a new candidate biomarker for colorectal cancer prognosis. OMICS. 2014;18:54–64.
Wang L, Mezencev R, Svajdler M, Benigno BB, McDonald JF. Ectopic over-expression of miR-429 induces mesenchymal-to-epithelial transition (MET) and increased drug sensitivity in metastasizing ovarian cancer cells. Gynecol Oncol. 2014;134:96–103.
Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, et al. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS ONE. 2014;9:e87780.
Sun T, Wang C, Xing J, Wu D. MiR-429 modulates the expression of c-myc in human gastric carcinoma cells. Eur J Cancer. 2011;47:2552–9.
Hu Q, Tong S, Zhao X, Ding W, Gou Y, Xu K, et al. Periostin mediates TGF-beta-induced epithelial mesenchymal transition in prostate cancer cells. Cell Physiol Biochem. 2015;36:799–809.
Sa Y, Li C, Li H, Guo H. TIMP-1 induces alpha-smooth muscle actin in fibroblasts to promote urethral scar formation. Cell Physiol Biochem. 2015;35:2233–43.
Lan A, Qi Y, Du J. Akt2 mediates TGF-beta1-induced epithelial to mesenchymal transition by deactivating GSK3beta/snail signaling pathway in renal tubular epithelial cells. Cell Physiol Biochem. 2014;34:368–82.
Teng Y, Zhao L, Zhang Y, Chen W, Li X. Id-1, a protein repressed by miR-29b, facilitates the TGFbeta1-induced epithelial-mesenchymal transition in human ovarian cancer cells. Cell Physiol Biochem. 2014;33:717–30.
Guo Y, Lang X, Lu Z, Wang J, Li T, Liao Y, et al. MiR-10b directly targets ZEB1 and PIK3CA to curb adenomyotic epithelial cell invasiveness via upregulation of e-cadherin and inhibition of Akt phosphorylation. Cell Physiol Biochem. 2015;35:2169–80.
Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28:151–66.
Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic Acids Res. 2013;41:W159–64.
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Prior patient’s consents and approval from the Institutional Research Ethics Committee of the Bethune International Peace Hospital were obtained for this study.
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Wei Liu and Jie An contributed equally to this work.
The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.
An erratum to this article is available at http://dx.doi.org/10.1007/s13277-017-5487-6.
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Liu, W., An, J., Li, K. et al. RETRACTED ARTICLE: MiR-429 regulates gastric cancer cell invasiveness through ZEB proteins. Tumor Biol. 37, 15575–15581 (2016). https://doi.org/10.1007/s13277-015-4094-7
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DOI: https://doi.org/10.1007/s13277-015-4094-7