miR-145 inhibits invasion and metastasis by directly targeting Smad3 in nasopharyngeal cancer
MicroRNA-145 (miR-145) has been implicated in several cancers. However, its role in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we proved that miR-145 was significantly downregulated in NPC and associated with NPC cell metastasis. Moreover, miR-145 suppressed Smad3 by directly binding to the 3′-untranslated region (UTR) of Smad3. Knockdown of Smad3 in NPC cells inhibited cell migration and invasion, which was consistent with the effect of miR-145 in NPC cells. In addition, Smad3 expression was inversely correlated with miR-145 level in clinical NPC samples. Taken together, our findings indicate that miR-145 is a tumour suppressor that affects invasive and metastatic properties of NPC via the miR-145/Smad3 axis, leading us to propose that miR-145 overexpression might be a potential therapeutic strategy of NPC intervention.
KeywordsmiR-145 Nasopharyngeal cancer Smad3 Invasion Metastasis
We would like to thank the Suzhou Key Laboratory for Molecular Cancer Genetics for their technical assistance. This work was supported by the Innovation Project of Suzhou International Technology Transfer and Cooperation (SH 201209), Suzhou Key Laboratory for Molecular Cancer Genetics (SZS201209) and Suzhou City’s Municipal Youth Fund of Science and Education (KJXW2012003).
Conflicts of interest
- 3.Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, et al. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80(3):661–8. doi: 10.1016/j.ijrobp.2010.03.024.CrossRefPubMedGoogle Scholar
- 17.Xiao J, Xiang Q, Xiao YC, Su ZJ, Huang ZF, Zhang QH, et al. The effect of transforming growth factor-beta1 on nasopharyngeal carcinoma cells: insensitive to cell growth but functional to TGF-beta/Smad pathway. J Exp Clin Cancer Res CR. 2010;29:35. doi: 10.1186/1756-9966-29-35.CrossRefPubMedGoogle Scholar
- 22.Thakur N, Gudey SK, Marcusson A, Fu JY, Bergh A, Heldin CH et al. TGFβ-induced invasion of prostate cancer cells is promoted by c-Jun-dependent transcriptional activation of Snail1. Cell cycle (Georgetown, Tex). 2014;13(15)Google Scholar
- 23.Yamazaki K, Masugi Y, Effendi K, Tsujikawa H, Hiraoka N, Kitago M, et al. Upregulated SMAD3 promotes epithelial-mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma. Lab Investig J Tech Methods Pathol. 2014;94(6):683–91. doi: 10.1038/labinvest.2014.53.CrossRefGoogle Scholar
- 26.Shen YA, Lin CH, Chi WH, Wang CY, Hsieh YT, Wei YH, et al. Resveratrol impedes the stemness, epithelial-mesenchymal transition, and metabolic reprogramming of cancer stem cells in nasopharyngeal carcinoma through p53 activation. Evid-Based Complement Alternat Med eCAM. 2013;2013:590393. doi: 10.1155/2013/590393.PubMedGoogle Scholar