The online version of this article (https://doi.org/10.1186/s12885-017-3875-3) contains supplementary material, which is available to authorized users.
EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis.
We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it’s mechanism.
Our analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0–G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, β-catenin, and Snail (markers of Wnt/β-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo.
miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.
Cancer Genome Atlas Research. N: comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. CrossRef
Puttick S, Stringer BW, Day BW, Bruce ZC, Ensbey KS, Mardon K, Cowin GJ, Thurecht KJ, Whittaker AK, Fay M, et al. EphA2 as a diagnostic imaging target in Glioblastoma: a positron emission tomography/magnetic resonance imaging study. Mol Imaging. 2015;14:385–99. PubMed
Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Normolle DP, Connelly AK, Dibridge S, Mason G, Whiteside TL, et al. Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas. Neuro-Oncology. 2016;18(8):1157–68. CrossRefPubMedPubMedCentral
Kurashige J, Mima K, Sawada G, Takahashi Y, Eguchi H, Sugimachi K, Mori M, Yanagihara K, Yashiro M, Hirakawa K, et al. Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer. Carcinogenesis. 2015;36(1):133–41. CrossRefPubMed
CB H, Li QL, JF H, Zhang Q, Xie JP, Deng L. miR-124 inhibits growth and invasion of gastric cancer by targeting ROCK1. Asian Pac J Cancer Prev. 2014;15(16):6543–6. CrossRef
Khalili M, Sadeghizadeh M, Ghorbanian K, Malekzadeh R, Vasei M, Mowla SJ. Down-regulation of miR-302b, an ESC-specific microRNA, in gastric adenocarcinoma. Cell J. 2012;13(4):251–8. PubMed
Hashiguchi Y, Nishida N, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Mochizuki H, Hase K, Doki Y, et al. Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance. Int J Oncol. 2012;40(5):1477–82. PubMed
WY W, Xue XY, Chen ZJ, Han SL, Huang YP, Zhang LF, Zhu GB, Shen X. Potentially predictive microRNAs of gastric cancer with metastasis to lymph node. World J Gastroenterol. 2011;17(31):3645–51. CrossRef
Antoon JW, Nitzchke AM, Martin EC, Rhodes LV, Nam S, Wadsworth S, Salvo VA, Elliott S, Collins-Burow B, Nephew KP, et al. Inhibition of p38 mitogen-activated protein kinase alters microRNA expression and reverses epithelial-to-mesenchymal transition. Int J Oncol. 2013;42(4):1139–50. CrossRefPubMedPubMedCentral
Li X, Luo F, Li Q, Xu M, Feng D, Zhang G, Wu W. Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep. 2011;26(6):1431–9. PubMed
Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90. PubMed
Liu FY, Wang LP, Wang Q, Han P, Zhuang WP, Li MJ, Yuan H. miR-302b regulates cell cycles by targeting CDK2 via ERK signaling pathway in gastric cancer. Cancer Med. 2016;
Mlcochova H, Machackova T, Rabien A, Radova L, Fabian P, Iliev R, Slaba K, Poprach A, Kilic E, Stanik M, et al. Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma. Sci Rep. 2016;6:31852. CrossRefPubMedPubMedCentral
- miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer
Howard L. Mcleod
- BioMed Central
Neu im Fachgebiet Onkologie
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