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Published in: Tumor Biology 10/2015

01-10-2015 | Research Article

MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by directly targeting F-box and WD-40 Domain Protein 7, FBXW7

Authors: Junhua Gong, Zheng Cui, Li Li, Qiang Ma, Qiufang Wang, Yinhe Gao, Hao Sun

Published in: Tumor Biology | Issue 10/2015

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Abstract

Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in tumorigenesis. MiR-25 was previously reported to act as tumor suppressor or oncogene in diverse cancers. However, their expression, function, and mechanism in gastric cancer (GC) are not well known. Here, we show that miR-25 was overexpressed in primary tumor tissues of GC patients and was significantly correlated with a more aggressive phenotype of GC in patients. MiR-25 inhibition significantly decreased the proliferation, invasion, and migration of GC cells in vitro. Furthermore, miR-25 repressed F-box and WD-40 domain protein 7 (FBXW7) expression by directly binding to 3-untranslated region (UTR) of FBXW7, and the inverse correlation was observed between the expressions of miR-25 and FBXW7 mRNA in primary GC tissues. Moreover, the restoration of FBXW7 led to suppressed proliferation, invasion, and migration of GC cells. In vivo, miR-25 promotes tumor growth of GC. Taken together, miR-25 promotes GC progression by directly downregulating FBXW7 expression and may be employed as a novel prognostic marker and therapeutic target of GC.
Literature
1.
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
4.
6.
go back to reference Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, et al. Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 2009;37:1672–81.CrossRefPubMedPubMedCentral Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, et al. Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 2009;37:1672–81.CrossRefPubMedPubMedCentral
7.
go back to reference Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, et al. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut. 2013;62:1315–26.CrossRefPubMed Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, et al. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut. 2013;62:1315–26.CrossRefPubMed
8.
go back to reference Wang X, Chen X, Wang R, Xiao P, Xu Z, Chen L, et al. MicroRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis. Oncol Rep. 2013;30:643–50.PubMed Wang X, Chen X, Wang R, Xiao P, Xu Z, Chen L, et al. MicroRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis. Oncol Rep. 2013;30:643–50.PubMed
9.
10.
go back to reference Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, Chang AN, Goel A, Yang HK. MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 2015;64:203–14. Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, Chang AN, Goel A, Yang HK. MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 2015;64:203–14.
11.
go back to reference Gong J, Li J, Wang Y, Liu C, Jia H, Jiang C, et al. Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis. 2014;35:497–506.CrossRefPubMed Gong J, Li J, Wang Y, Liu C, Jia H, Jiang C, et al. Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis. 2014;35:497–506.CrossRefPubMed
12.
go back to reference Qiao F, Zhang K, Gong P, Wang L, Hu J, Lu S, et al. Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis. Mol Biol Rep. 2014;41:5693–700.CrossRefPubMed Qiao F, Zhang K, Gong P, Wang L, Hu J, Lu S, et al. Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis. Mol Biol Rep. 2014;41:5693–700.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9:824–33.CrossRefPubMed Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9:824–33.CrossRefPubMed
15.
go back to reference Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, et al. The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. Gastroenterology. 2009;136:1689–700.CrossRefPubMedPubMedCentral Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, et al. The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. Gastroenterology. 2009;136:1689–700.CrossRefPubMedPubMedCentral
16.
go back to reference Li BS, Zuo QF, Zhao YL, Xiao B, Zhuang Y, Mao XH, Wu C, Yang SM, Zeng H, Zou QM, Guo G: MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival. Oncogene. 2014;34:2474–83. Li BS, Zuo QF, Zhao YL, Xiao B, Zhuang Y, Mao XH, Wu C, Yang SM, Zeng H, Zou QM, Guo G: MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival. Oncogene. 2014;34:2474–83.
17.
go back to reference Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83–93.CrossRefPubMed Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83–93.CrossRefPubMed
18.
go back to reference Cheng Y, Li G. Role of the ubiquitin ligase Fbw7 in cancer progression. Cancer Metastasis Rev. 2012;31:75–87.CrossRefPubMed Cheng Y, Li G. Role of the ubiquitin ligase Fbw7 in cancer progression. Cancer Metastasis Rev. 2012;31:75–87.CrossRefPubMed
19.
go back to reference Brandt Y, Mitchell T, Wu Y, Hartley RS. Developmental downregulation of Xenopus cyclin E is phosphorylation and nuclear import dependent and is mediated by ubiquitination. Dev Biol. 2011;355:65–76.CrossRefPubMedPubMedCentral Brandt Y, Mitchell T, Wu Y, Hartley RS. Developmental downregulation of Xenopus cyclin E is phosphorylation and nuclear import dependent and is mediated by ubiquitination. Dev Biol. 2011;355:65–76.CrossRefPubMedPubMedCentral
20.
go back to reference Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001;294:173–7.CrossRefPubMed Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001;294:173–7.CrossRefPubMed
21.
go back to reference Milne AN, Leguit R, Corver WE, Morsink FH, Polak M, de Leng WW, et al. Loss of CDC4/FBXW7 in gastric carcinoma. Cell Oncol. 2010;32:347–59.PubMedPubMedCentral Milne AN, Leguit R, Corver WE, Morsink FH, Polak M, de Leng WW, et al. Loss of CDC4/FBXW7 in gastric carcinoma. Cell Oncol. 2010;32:347–59.PubMedPubMedCentral
22.
go back to reference Li J, Guo Y, Liang X, Sun M, Wang G, De W, et al. MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J Cancer Res Clin Oncol. 2012;138:763–74.CrossRefPubMed Li J, Guo Y, Liang X, Sun M, Wang G, De W, et al. MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J Cancer Res Clin Oncol. 2012;138:763–74.CrossRefPubMed
23.
go back to reference Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRefPubMed Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRefPubMed
24.
go back to reference Matuszcak C, Haier J, Hummel R, Lindner K. MicroRNAs: promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential. World J Gastroenterol. 2014;20:13658–66.CrossRefPubMedPubMedCentral Matuszcak C, Haier J, Hummel R, Lindner K. MicroRNAs: promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential. World J Gastroenterol. 2014;20:13658–66.CrossRefPubMedPubMedCentral
26.
go back to reference Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR, et al. MiR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology. 2012;55:465–75.CrossRefPubMed Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR, et al. MiR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology. 2012;55:465–75.CrossRefPubMed
27.
go back to reference Brett JO, Renault VM, Rafalski VA, Webb AE, Brunet A. The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY). 2011;3:108–24.CrossRef Brett JO, Renault VM, Rafalski VA, Webb AE, Brunet A. The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY). 2011;3:108–24.CrossRef
28.
go back to reference Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. 2013;335:168–74.CrossRefPubMed Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. 2013;335:168–74.CrossRefPubMed
29.
go back to reference Esposito F, Tornincasa M, Pallante P, Federico A, Borbone E, Pierantoni GM, et al. Down-regulation of the miR-25 and miR-30d contributes to the development of anaplastic thyroid carcinoma targeting the polycomb protein EZH2. J Clin Endocrinol Metab. 2012;97:E710–8.CrossRefPubMed Esposito F, Tornincasa M, Pallante P, Federico A, Borbone E, Pierantoni GM, et al. Down-regulation of the miR-25 and miR-30d contributes to the development of anaplastic thyroid carcinoma targeting the polycomb protein EZH2. J Clin Endocrinol Metab. 2012;97:E710–8.CrossRefPubMed
30.
go back to reference Mao JH, Perez-Losada J, Wu D, Delrosario R, Tsunematsu R, Nakayama KI, et al. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature. 2004;432:775–9.CrossRefPubMed Mao JH, Perez-Losada J, Wu D, Delrosario R, Tsunematsu R, Nakayama KI, et al. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature. 2004;432:775–9.CrossRefPubMed
31.
go back to reference Hagedorn M, Delugin M, Abraldes I, Allain N, Belaud-Rotureau MA, Turmo M, et al. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients. Cell Div. 2007;2:9.CrossRefPubMedPubMedCentral Hagedorn M, Delugin M, Abraldes I, Allain N, Belaud-Rotureau MA, Turmo M, et al. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients. Cell Div. 2007;2:9.CrossRefPubMedPubMedCentral
32.
go back to reference Gu Z, Inomata K, Ishizawa K, Horii A. The FBXW7 beta-form is suppressed in human glioma cells. Biochem Biophys Res Commun. 2007;354:992–8.CrossRefPubMed Gu Z, Inomata K, Ishizawa K, Horii A. The FBXW7 beta-form is suppressed in human glioma cells. Biochem Biophys Res Commun. 2007;354:992–8.CrossRefPubMed
33.
go back to reference Iwatsuki M, Mimori K, Ishii H, Yokobori T, Takatsuno Y, Sato T, et al. Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: clinical significance. Int J Cancer. 2010;126:1828–37.PubMed Iwatsuki M, Mimori K, Ishii H, Yokobori T, Takatsuno Y, Sato T, et al. Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: clinical significance. Int J Cancer. 2010;126:1828–37.PubMed
34.
go back to reference Lu D, Davis MP, Abreu-Goodger C, Wang W, Campos LS, Siede J, et al. MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs. PLoS One. 2012;7:e40938.CrossRefPubMedPubMedCentral Lu D, Davis MP, Abreu-Goodger C, Wang W, Campos LS, Siede J, et al. MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs. PLoS One. 2012;7:e40938.CrossRefPubMedPubMedCentral
Metadata
Title
MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by directly targeting F-box and WD-40 Domain Protein 7, FBXW7
Authors
Junhua Gong
Zheng Cui
Li Li
Qiang Ma
Qiufang Wang
Yinhe Gao
Hao Sun
Publication date
01-10-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 10/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3510-3

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