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Published in: Clinical and Translational Oncology 3/2014

01-03-2014 | Research Article

Microvesicle microRNA profiles and functional roles between chronic hepatitis B and hepatocellular carcinoma

Authors: H. Li, L. Sun, X. Chen, W. Xiong, D. Hu, S. Jie

Published in: Clinical and Translational Oncology | Issue 3/2014

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Abstract

Objectives

Hepatocellular carcinoma (HCC) is an inflammation-related malignancy and chronic hepatitis B (CHB) predisposes to HCC. Microvesicles (MVs) transfer various bioactive molecules including microRNA (miRNA) between cells and exert biological functions. The purpose of this study was to detect CHB-MV and HCC-MV miRNAs and analyze the expression profiles and functional roles between CHB and HCC.

Methods

We examined MV miRNA profiles of CHB and HCC using miRNA microarrays. TargetScan, PicTar and miRanda were exerted to predict target genes regulating these differentially expressed miRNAs.

Results

A total of 272 and 242 aberrant fluctuation miRNAs were identified in CHB-MVs and HCC-MVs, respectively. Among them, there were 53 miRNAs co-expressing both in CHB-MVs and HCC-MVs. These miRNAs affected cellular apoptosis, proliferation and molecular signaling pathways. Among them, 25 co-expressed MV miRNAs targeted 21 inflammatory factors and these miRNAs may be a tight linkage between CHB and HCC. Interestingly, there were 14 co-expressed MV miRNAs targeting 17 oncogenes and 7 miRNAs targeting 9 tumor suppressors in the study. In addition, MVs were enriched with maladjusted miRNAs regulating zinc finger proteins and chromosome open reading frame. Those MV miRNAs may play roles in CHB developing to HCC.

Conclusions

We demonstrated that CHB and HCC displayed aberrantly co-expressed MV miRNA profiles for the first time, which may have a link between CHB and HCC. Those MV miRNAs may serve as early biomarkers for HCC and may aid to promote CHB developing to HCC.
Literature
1.
go back to reference Block TM, Mehta AS, Fimmel CJ, Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene. 2003;22:5093–107.PubMedCrossRef Block TM, Mehta AS, Fimmel CJ, Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene. 2003;22:5093–107.PubMedCrossRef
3.
go back to reference Poehlmann A, Kuester D, Malfertheiner P, Guenther T, Roessner A. Inflammation and Barrett’s carcinogenesis. Pathol Res Pract. 2012;208:269–80.PubMedCrossRef Poehlmann A, Kuester D, Malfertheiner P, Guenther T, Roessner A. Inflammation and Barrett’s carcinogenesis. Pathol Res Pract. 2012;208:269–80.PubMedCrossRef
4.
go back to reference Liao R, Sun TW, Yi Y, Wu H, Li YW, Wang JX, et al. Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma. Cancer Sci. 2012;103:984–92.PubMedCrossRef Liao R, Sun TW, Yi Y, Wu H, Li YW, Wang JX, et al. Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma. Cancer Sci. 2012;103:984–92.PubMedCrossRef
5.
go back to reference Benameur T, Andriantsitohaina R, Martínez MC. Therapeutic potential of plasma membrane-derived microparticles. Pharmacol Rep. 2009;61:49–57.PubMed Benameur T, Andriantsitohaina R, Martínez MC. Therapeutic potential of plasma membrane-derived microparticles. Pharmacol Rep. 2009;61:49–57.PubMed
6.
go back to reference Gyorgy B, Szabo TG, Pasztoi M, Pal Z, Misjak P, Aradi B, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68:2667–88.PubMedCentralPubMedCrossRef Gyorgy B, Szabo TG, Pasztoi M, Pal Z, Misjak P, Aradi B, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68:2667–88.PubMedCentralPubMedCrossRef
7.
go back to reference Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular ‘debris’. Semin Immunopathol. 2011;33:455–67.PubMedCrossRef Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular ‘debris’. Semin Immunopathol. 2011;33:455–67.PubMedCrossRef
8.
go back to reference Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907–20.PubMedCrossRef Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907–20.PubMedCrossRef
9.
go back to reference Simons M, Raposo G. Exosomes-vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575–81.PubMedCrossRef Simons M, Raposo G. Exosomes-vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575–81.PubMedCrossRef
10.
11.
go back to reference Dalli J, Norling LV, Renshaw D, Cooper D, Leung KY, Perretti M, et al. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood. 2008;112:2512–9.PubMedCrossRef Dalli J, Norling LV, Renshaw D, Cooper D, Leung KY, Perretti M, et al. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood. 2008;112:2512–9.PubMedCrossRef
12.
go back to reference Schetter AJ, Heegaard NH, Harris CC. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 2010;31:37–49.PubMedCrossRef Schetter AJ, Heegaard NH, Harris CC. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 2010;31:37–49.PubMedCrossRef
13.
go back to reference Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, et al. Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond). 2011;120:183–93.CrossRef Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, et al. Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond). 2011;120:183–93.CrossRef
14.
go back to reference Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE. 2008;3:e3694.PubMedCentralPubMedCrossRef Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE. 2008;3:e3694.PubMedCentralPubMedCrossRef
15.
go back to reference Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–73.PubMedCrossRef Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–73.PubMedCrossRef
16.
go back to reference Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N, et al. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455:58–63.PubMedCrossRef Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N, et al. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455:58–63.PubMedCrossRef
18.
go back to reference Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.PubMedCrossRef Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.PubMedCrossRef
19.
go back to reference Han YF, Zhao J, Ma LY, Yin JH, Chang WJ, Zhang HW, et al. Factors predicting occurrence and prognosis of hepatitis- B-virus-related hepatocellular carcinoma. World J Gastroenterol. 2011;17:4258–70.PubMedCrossRef Han YF, Zhao J, Ma LY, Yin JH, Chang WJ, Zhang HW, et al. Factors predicting occurrence and prognosis of hepatitis- B-virus-related hepatocellular carcinoma. World J Gastroenterol. 2011;17:4258–70.PubMedCrossRef
20.
go back to reference Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y. Cytokines in cancer immunity and immunotherapy. Immunol Rev. 2004;202:275–93.PubMedCrossRef Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y. Cytokines in cancer immunity and immunotherapy. Immunol Rev. 2004;202:275–93.PubMedCrossRef
21.
go back to reference Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.PubMedCrossRef Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.PubMedCrossRef
23.
go back to reference Chen L, Zhang Q, Chang W, Du Y, Zhang H, Cao G. Viral and host inflammation-related factorsthat can predict the prognosis of hepatocellular carcinoma. Eur J Cancer. 2012;48:1977–87.PubMedCrossRef Chen L, Zhang Q, Chang W, Du Y, Zhang H, Cao G. Viral and host inflammation-related factorsthat can predict the prognosis of hepatocellular carcinoma. Eur J Cancer. 2012;48:1977–87.PubMedCrossRef
24.
go back to reference Fan HB, Guo YB, Wang BJ, Zhu YF, Wu AH, Hou JL, et al. Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:979–81.PubMed Fan HB, Guo YB, Wang BJ, Zhu YF, Wu AH, Hou JL, et al. Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:979–81.PubMed
25.
go back to reference Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2:e000825.PubMedCentralPubMedCrossRef Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2:e000825.PubMedCentralPubMedCrossRef
26.
go back to reference Zhao A, Zeng Q, Xie X, Zhou J, Yue W, Li Y, et al. MicroRNA-125b induces cancer cell apoptosis through suppression of Bcl-2 expression. J Genet Genomics. 2012;39:29–35.PubMedCrossRef Zhao A, Zeng Q, Xie X, Zhou J, Yue W, Li Y, et al. MicroRNA-125b induces cancer cell apoptosis through suppression of Bcl-2 expression. J Genet Genomics. 2012;39:29–35.PubMedCrossRef
27.
go back to reference Wang WH, Studach LL, Andrisani OM. Proteins ZNF198 and SUZ12 are down-regulated in hepatitis B virus (HBV) X protein-mediated hepatocyte transformation and in HBV replication. Hepatology. 2011;53:1137–47.PubMedCentralPubMedCrossRef Wang WH, Studach LL, Andrisani OM. Proteins ZNF198 and SUZ12 are down-regulated in hepatitis B virus (HBV) X protein-mediated hepatocyte transformation and in HBV replication. Hepatology. 2011;53:1137–47.PubMedCentralPubMedCrossRef
28.
go back to reference Hu HM, Chen Y, Liu L, Zhang CG, Wang W, Gong K, et al. C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is associated with tumorigenesis and metastasis. FASEB J. 2013;27:163–73.PubMedCrossRef Hu HM, Chen Y, Liu L, Zhang CG, Wang W, Gong K, et al. C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is associated with tumorigenesis and metastasis. FASEB J. 2013;27:163–73.PubMedCrossRef
29.
go back to reference Sakai M, Shimokawa T, Kobayashi T, Matsushima S, Yamada Y, Nakamura Y, et al. Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor. Oncogene. 2006;25:480–6.PubMed Sakai M, Shimokawa T, Kobayashi T, Matsushima S, Yamada Y, Nakamura Y, et al. Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor. Oncogene. 2006;25:480–6.PubMed
30.
go back to reference Jing Z, Yuan X, Zhang J, Huang X, Zhang Z, Liu J, et al. Chromosome 1 open reading frame 190 promotes activation of NF-κB canonical pathway and resistance of dendritic cells to tumor-associated inhibition in vitro. J Immunol. 2010;185:6719–27.PubMedCrossRef Jing Z, Yuan X, Zhang J, Huang X, Zhang Z, Liu J, et al. Chromosome 1 open reading frame 190 promotes activation of NF-κB canonical pathway and resistance of dendritic cells to tumor-associated inhibition in vitro. J Immunol. 2010;185:6719–27.PubMedCrossRef
Metadata
Title
Microvesicle microRNA profiles and functional roles between chronic hepatitis B and hepatocellular carcinoma
Authors
H. Li
L. Sun
X. Chen
W. Xiong
D. Hu
S. Jie
Publication date
01-03-2014
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 3/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1078-1

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