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Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor

Authors: Kejia Wang, Qing Liang, Li Wei, Wei Zhang, Ping Zhu

Published in: Tumor Biology | Issue 3/2016

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Abstract

Human hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Research on HCC has recently focused on microRNAs (miRNAs) that play crucial roles in cancer development and progression of HCC. In this study, we aimed to analyze the expression and function of a metastasis-associated microRNA-608 (miR-608) in HCC. Samples of human HCC and matched adjacent normal tissues were surgically removed, and miR-608 expression and the pathological characteristics of HCC were investigated. In this study, we found that miR-608 expression was significantly reduced in HCC and its expression levels were highly associated with tumor size, differentiation, clinical stage, and overall and disease-free survival of HCC. Overexpression of miR-608 in HCC cell lines HepG2 and SK-Hep-1 inhibited cell proliferation by G1 arrest. Macrophage migration inhibitory factor (MIF), a potential target gene of miR-608, was inversely correlated with miR-608 expression in HCC tissues and cell lines. Furthermore, we demonstrated that MIF was directly regulated by miR-608 and the restoration of MIF expression reversed the inhibitory effects of miR-608 on HCC cell proliferation. Taken together, these findings collectively demonstrate that miR-608 exerts its anti-cancer function by directly targeting MIF in HCC, indicating a potential novel prognostic biomarker and therapeutic target for HCC.
Literature
1.
go back to reference Huntzicker EG, Hotzel K, Choy L, Che L, Ross J, Pau G, et al. Differential effects of targeting notch receptors in a mouse model of liver cancer. Hepatology. 2015;61:942–52.CrossRefPubMedPubMedCentral Huntzicker EG, Hotzel K, Choy L, Che L, Ross J, Pau G, et al. Differential effects of targeting notch receptors in a mouse model of liver cancer. Hepatology. 2015;61:942–52.CrossRefPubMedPubMedCentral
2.
go back to reference Chen Z, Huang Z, Ye Q, Ming Y, Zhang S, Zhao Y, et al. Prognostic significance and anti-proliferation effect of microRNA-365 in hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8:1705–11.PubMedPubMedCentral Chen Z, Huang Z, Ye Q, Ming Y, Zhang S, Zhao Y, et al. Prognostic significance and anti-proliferation effect of microRNA-365 in hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8:1705–11.PubMedPubMedCentral
3.
go back to reference Ho C, Wang C, Mattu S, Destefanis G, Ladu S, Delogu S, et al. Akt (v-akt murine thymoma viral oncogene homolog 1) and n-ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mtor (mammalian target of rapamycin complex 1), foxm1 (forkhead box m1)/skp2, and c-myc pathways. Hepatology. 2012;55:833–45.CrossRefPubMed Ho C, Wang C, Mattu S, Destefanis G, Ladu S, Delogu S, et al. Akt (v-akt murine thymoma viral oncogene homolog 1) and n-ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mtor (mammalian target of rapamycin complex 1), foxm1 (forkhead box m1)/skp2, and c-myc pathways. Hepatology. 2012;55:833–45.CrossRefPubMed
4.
go back to reference El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.CrossRefPubMed El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.CrossRefPubMed
5.
go back to reference Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, et al. Therapeutic antibody targeting of individual notch receptors. Nature. 2010;464:1052–7.CrossRefPubMed Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, et al. Therapeutic antibody targeting of individual notch receptors. Nature. 2010;464:1052–7.CrossRefPubMed
6.
go back to reference Huang X, Qin J, Lu S. Up-regulation of mir-877 induced by paclitaxel inhibits hepatocellular carcinoma cell proliferation though targeting foxm1. Int J Clin Exp Pathol. 2015;8:1515–24.PubMedPubMedCentral Huang X, Qin J, Lu S. Up-regulation of mir-877 induced by paclitaxel inhibits hepatocellular carcinoma cell proliferation though targeting foxm1. Int J Clin Exp Pathol. 2015;8:1515–24.PubMedPubMedCentral
7.
go back to reference Wang X, Zhang J, Zhou L, Lu P, Zheng ZG, Sun W, et al. Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): clinical analyses of patients and an HCC rat model. Int J Clin Exp Pathol. 2015;8:1466–78.PubMedPubMedCentral Wang X, Zhang J, Zhou L, Lu P, Zheng ZG, Sun W, et al. Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): clinical analyses of patients and an HCC rat model. Int J Clin Exp Pathol. 2015;8:1466–78.PubMedPubMedCentral
8.
go back to reference Dou C, Wang Y, Li C, Liu Z, Jia Y, Li Q, Yang W, Yao Y, Liu Q, Tu K. Microrna-212 suppresses tumor growth of human hepatocellular carcinoma by targeting FOXA1. Oncotarget. 2015. Dou C, Wang Y, Li C, Liu Z, Jia Y, Li Q, Yang W, Yao Y, Liu Q, Tu K. Microrna-212 suppresses tumor growth of human hepatocellular carcinoma by targeting FOXA1. Oncotarget. 2015.
10.
go back to reference Garzon R, Marcucci G. Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr Opin Oncol. 2012;24:655–9.CrossRefPubMed Garzon R, Marcucci G. Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr Opin Oncol. 2012;24:655–9.CrossRefPubMed
11.
go back to reference Wang G, Sun Y, He Y, Ji C, Hu B, Sun Y. MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box p4 (foxp4). Int J Clin Exp Pathol. 2015;8:337–44.PubMedPubMedCentral Wang G, Sun Y, He Y, Ji C, Hu B, Sun Y. MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box p4 (foxp4). Int J Clin Exp Pathol. 2015;8:337–44.PubMedPubMedCentral
12.
go back to reference Xiao ZD, Jiao CY, Huang HT, He LJ, Zhao JJ, Lu ZY, et al. Mir-218 modulate hepatocellular carcinoma cell proliferation through pten/akt/pi3k pathway and hoxa10. Int J Clin Exp Pathol. 2014;7:4039–44.PubMedPubMedCentral Xiao ZD, Jiao CY, Huang HT, He LJ, Zhao JJ, Lu ZY, et al. Mir-218 modulate hepatocellular carcinoma cell proliferation through pten/akt/pi3k pathway and hoxa10. Int J Clin Exp Pathol. 2014;7:4039–44.PubMedPubMedCentral
13.
go back to reference Chang RM, Yang H, Fang F, Xu JF, Yang LY. MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting ph domain and leucine-rich repeat protein phosphatase. Hepatology. 2014;60:1251–63.CrossRefPubMed Chang RM, Yang H, Fang F, Xu JF, Yang LY. MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting ph domain and leucine-rich repeat protein phosphatase. Hepatology. 2014;60:1251–63.CrossRefPubMed
14.
go back to reference Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2010;42:1273–81.CrossRefPubMed Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2010;42:1273–81.CrossRefPubMed
15.
go back to reference Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013;57:840–7.CrossRefPubMed Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013;57:840–7.CrossRefPubMed
16.
go back to reference Qiu F, Yang L, Zhang L, Yang X, Yang R, Fang W, et al. Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma. Gene. 2015;565:180–6.CrossRefPubMed Qiu F, Yang L, Zhang L, Yang X, Yang R, Fang W, et al. Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma. Gene. 2015;565:180–6.CrossRefPubMed
17.
go back to reference Pardini B, Rosa F, Naccarati A, Vymetalkova V, Ye Y, Wu X, et al. Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis. 2015;36:82–6.CrossRefPubMed Pardini B, Rosa F, Naccarati A, Vymetalkova V, Ye Y, Wu X, et al. Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis. 2015;36:82–6.CrossRefPubMed
20.
go back to reference Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun. 2011;405:153–6.CrossRefPubMed Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun. 2011;405:153–6.CrossRefPubMed
21.
go back to reference Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting egfr, bcl-xl and met. PLoS One. 2014;9, e91546.CrossRefPubMedPubMedCentral Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting egfr, bcl-xl and met. PLoS One. 2014;9, e91546.CrossRefPubMedPubMedCentral
22.
go back to reference Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol. 2012;59:467–74.PubMed Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol. 2012;59:467–74.PubMed
23.
go back to reference Adamali H, Armstrong ME, McLaughlin AM, Cooke G, McKone E, Costello CM, et al. Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. Am J Respir Crit Care Med. 2012;186:162–9.CrossRefPubMed Adamali H, Armstrong ME, McLaughlin AM, Cooke G, McKone E, Costello CM, et al. Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. Am J Respir Crit Care Med. 2012;186:162–9.CrossRefPubMed
24.
go back to reference Tas F, Karabulut S, Serilmez M, Ciftci R, Duranyildiz D. Serum levels of macrophage migration-inhibitory factor (MIF) have diagnostic, predictive and prognostic roles in epithelial ovarian cancer patients. Tumour Biol: J Int Soc Oncodev Biol Med. 2014;35:3327–31.CrossRef Tas F, Karabulut S, Serilmez M, Ciftci R, Duranyildiz D. Serum levels of macrophage migration-inhibitory factor (MIF) have diagnostic, predictive and prognostic roles in epithelial ovarian cancer patients. Tumour Biol: J Int Soc Oncodev Biol Med. 2014;35:3327–31.CrossRef
25.
go back to reference Tan L, Ye X, Zhou Y, Yu M, Fu Z, Chen R, et al. Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of beta-cell. J Transl Med. 2014;12:92.CrossRefPubMedPubMedCentral Tan L, Ye X, Zhou Y, Yu M, Fu Z, Chen R, et al. Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of beta-cell. J Transl Med. 2014;12:92.CrossRefPubMedPubMedCentral
26.
go back to reference Richard V, Kindt N, Decaestecker C, Gabius HJ, Laurent G, Noel JC, et al. Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer. Oncol Rep. 2014;32:523–9.PubMedPubMedCentral Richard V, Kindt N, Decaestecker C, Gabius HJ, Laurent G, Noel JC, et al. Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer. Oncol Rep. 2014;32:523–9.PubMedPubMedCentral
27.
go back to reference Pei XJ, Wu TT, Li B, Tian XY, Li Z, Yang QX. Increased expression of macrophage migration inhibitory factor and dj-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma. Int J Med Sci. 2014;11:106–15.CrossRefPubMedPubMedCentral Pei XJ, Wu TT, Li B, Tian XY, Li Z, Yang QX. Increased expression of macrophage migration inhibitory factor and dj-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma. Int J Med Sci. 2014;11:106–15.CrossRefPubMedPubMedCentral
28.
go back to reference Oliveira CS, de Bock CE, Molloy TJ, Sadeqzadeh E, Geng XY, Hersey P, et al. Macrophage migration inhibitory factor engages pi3k/akt signalling and is a prognostic factor in metastatic melanoma. BMC Cancer. 2014;14:630.CrossRefPubMedPubMedCentral Oliveira CS, de Bock CE, Molloy TJ, Sadeqzadeh E, Geng XY, Hersey P, et al. Macrophage migration inhibitory factor engages pi3k/akt signalling and is a prognostic factor in metastatic melanoma. BMC Cancer. 2014;14:630.CrossRefPubMedPubMedCentral
29.
go back to reference Ren Y, Tsui HT, Poon RT, Ng IO, Li Z, Chen Y, et al. Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma. Int J Cancer. 2003;107:22–9.CrossRefPubMed Ren Y, Tsui HT, Poon RT, Ng IO, Li Z, Chen Y, et al. Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma. Int J Cancer. 2003;107:22–9.CrossRefPubMed
30.
go back to reference Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, et al. Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer. 2005;103:588–98.CrossRefPubMed Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, et al. Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer. 2005;103:588–98.CrossRefPubMed
31.
go back to reference Xia JT, Li W, Liu YJ, Chen LZ, Wu ZF, Zhang LJ, et al. Correlations of expressions of macrophage migration inhibitor factor and cyclin D1 with tumor size and metastasis of hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2007;15:918–21.PubMed Xia JT, Li W, Liu YJ, Chen LZ, Wu ZF, Zhang LJ, et al. Correlations of expressions of macrophage migration inhibitor factor and cyclin D1 with tumor size and metastasis of hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2007;15:918–21.PubMed
32.
go back to reference Huang XH, Jian WH, Wu ZF, Zhao J, Wang H, Li W, et al. Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation. Oncotarget. 2014;5:5570–80.CrossRefPubMedPubMedCentral Huang XH, Jian WH, Wu ZF, Zhao J, Wang H, Li W, et al. Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation. Oncotarget. 2014;5:5570–80.CrossRefPubMedPubMedCentral
Metadata
Title
MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor
Authors
Kejia Wang
Qing Liang
Li Wei
Wei Zhang
Ping Zhu
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4213-5

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