The human leukocyte antigen f-associated transcript 10 (FAT10) has a similar structure and function with ubiquitin, which efficiently mediate proteasome degradation in an ubiquitin-independent manner. FAT10 expression is upregulated in many tumor tissues and plays a vital role in cell cycle regulation and tumor genesis. However, its role in glioma has not been illuminated. The aim of this study was to evaluate the prognostic value of FAT10 and investigate its functional roles in glioma. The expression of FAT10 in glioma patient samples was examined using quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry methods. Glioma cell lines with either FAT10 overexpression or knockdown were created. The effect of FAT10 on glioma cell migration and invasion was investigated using these cells. In the present study, we had shown that FAT10 was elevated significantly in glioma samples and correlated with tumor pathological grade. FAT10 high-expression glioma is associated with a poor clinical prognosis. Overexpression of FAT10 promoted proliferation, invasion, migration, and sphere formation of glioma cells, whereas downregulation of FAT10 had an opposite effect. Overexpression of FAT10 also promoted the growth of glioma cells in vivo. Moreover, FAT10 enhanced the phosphorylation of Smad2, which contributes to FAT10-induced oncogenic activities in glioma. In conclusion, these findings indicate that FAT10 is a critical regulator potential therapeutic target of glioma.
FAT10 Glioma Smad2 Proliferation
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This work was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2013BAI09B03).
Compliance with ethical standards
All patients gave informed consent for the analyses to be undertaken, and the study protocol was approved by the Ethical Committee of the coordinating center, the Capital Medical University (Decision no. CMU-201409). Animal handling and research protocols were approved by the Animal Care and Use Ethnic Committee of Capital Medical University, Beijing China (Decision no. CMU-201410).
Zhang X, Chen T, Zhang J, Mao Q, Li S, Xiong W, et al. Notch1 promotes glioma cell migration and invasion by stimulating beta-catenin and NF-kappaB signaling via AKT activation. Cancer Sci. 2012;103(2):181–90.CrossRefPubMedGoogle Scholar
Isaacson MK, Ploegh HL. Ubiquitination, ubiquitin-like modifiers, and deubiquitination in viral infection. Cell Host Microbe. 2009;5(6):559–70.CrossRefPubMedGoogle Scholar
Ren J, Kan A, Leong SH, Ooi LL, Jeang KT, Chong SS, et al. FAT10 plays a role in the regulation of chromosomal stability. J Biol Chem. 2006;281(16):11413–21.CrossRefPubMedGoogle Scholar
Li T, Santockyte R, Yu S, Shen RF, Tekle E, Lee CG, et al. FAT10 modifies p53 and upregulates its transcriptional activity. Arch Biochem Biophys. 2011;509(2):164–9.CrossRefPubMedPubMedCentralGoogle Scholar
Ji F, Jin X, Jiao CH, Xu QW, Wang ZW, Chen YL. FAT10 level in human gastric cancer and its relation with mutant p53 level, lymph node metastasis and TNM staging. World J Gastroenterol. 2009;15(18):2228–33.CrossRefPubMedPubMedCentralGoogle Scholar
Yuan J, Tu Y, Mao X, He S, Wang L, Fu G, et al. Increased expression of FAT10 is correlated with progression and prognosis of human glioma. Pathol Oncol Res. 2012;18(4):833–9.CrossRefPubMedGoogle Scholar
Liu L, Dong Z, Liang J, Cao C, Sun J, Ding Y, et al. As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3beta pathway. Oncogene. 2014;33(7):909–20.CrossRefPubMedGoogle Scholar
Wang Y, Wen M, Kwon Y, Xu Y, Liu Y, Zhang P, et al. CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression. Cancer Res. 2014;74(2):520–31.CrossRefPubMedGoogle Scholar
Sun Y, Wang Y, Fan C, Gao P, Wang X, Wei G, et al. Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells through Gli1 activation. Mol Cancer. 2014;13:137.CrossRefPubMedPubMedCentralGoogle Scholar
Theng SS, Wang W, Mah WC, Chan C, Zhuo J, Gao Y, et al. Disruption of FAT10-MAD2 binding inhibits tumor progression. Proc Natl Acad Sci U S A. 2014;111(49):E5282–91.CrossRefPubMedPubMedCentralGoogle Scholar
Yuan R, Wang K, Hu J, Yan C, Li M, Yu X, et al. Ubiquitin-like protein FAT10 promotes the invasion and metastasis of hepatocellular carcinoma by modifying beta-catenin degradation. Cancer Res. 2014;74(18):5287–300.CrossRefPubMedGoogle Scholar
Lukasiak S, Schiller C, Oehlschlaeger P, Schmidtke G, Krause P, Legler DF, et al. Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon. Oncogene. 2008;27(46):6068–74.CrossRefPubMedGoogle Scholar
Canaan A, DeFuria J, Perelman E, Schultz V, Seay M, Tuck D, et al. Extended lifespan and reduced adiposity in mice lacking the FAT10 gene. Proc Natl Acad Sci U S A. 2014;111(14):5313–8.CrossRefPubMedPubMedCentralGoogle Scholar
Liang X, Zeng J, Wang L, Shen L, Ma X, Li S, et al. Histone demethylase RBP2 promotes malignant progression of gastric cancer through TGF-beta1-(p-Smad3)-RBP2-E-cadherin-Smad3 feedback circuit. Oncotarget. 2015;6(19):17661–74.CrossRefPubMedPubMedCentralGoogle Scholar
Jennings MT, Pietenpol JA. The role of transforming growth factor beta in glioma progression. J Neurooncol. 1998;36(2):123–40.CrossRefPubMedGoogle Scholar