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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

A microRNA profile associated with Opisthorchis viverrini-induced cholangiocarcinoma in tissue and plasma

Authors: Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasite Opisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically normal tissue adjacent to ICC tumor displayed miRNA expression profiles more similar to tumor than liver tissue from healthy donors. In plasma samples, an eight-miRNA signature associated with ICC, regardless of the degree of histological differentiation of its matched tissue, forming the basis of a circulating miRNA-based biomarker for ICC.

Conclusions

The association of unique miRNA profiles with different ICC subtypes suggests the involvement of specific miRNAs during ICC tumor progression. In plasma, an eight-miRNA signature associated with ICC could form the foundation of an accessible (plasma-based) miRNA-based biomarker for the early detection of ICC.
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Literature
1.
Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet. 2005;366:1303–14.CrossRefPubMed
2.
Sripa B, Bethony JM, Sithithaworn P, Kaewkes S, Mairiang E, Loukas A, et al. Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Trop. 2011;120 Suppl 1:S158–68.CrossRefPubMed
3.
4.
IARC. Schistosomes, liver flukes and helicobacter pylori. IARC monographs on the evaluation of carcinogenic risks to humans. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol. volume 61. Lyon: IARC; 1994. p. 218–21.
5.
Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, et al. The tumorigenic liver fluke Opisthorchis viverrini–multiple pathways to cancer. Trends Parasitol. 2012;28:395–407.CrossRefPubMedPubMedCentral
6.
7.
8.
9.
Wang S, Yin J, Li T, Yuan L, Wang D, He J, et al. Upregulated circulating miR-150 is associated with the risk of intrahepatic cholangiocarcinoma. Oncol Rep. 2015;33:819–25.PubMed
10.
Chusorn P, Namwat N, Loilome W, Techasen A, Pairojkul C, Khuntikeo N, et al. Overexpression of microRNA-21 regulating PDCD4 during tumorigenesis of liver fluke-associated cholangiocarcinoma contributes to tumor growth and metastasis. Tumour Biol. 2013;34:1579–88.CrossRefPubMed
11.
12.
Plieskatt JL, Rinaldi G, Feng Y, Peng J, Yonglitthipagon P, Easley S, et al. Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini. J Hepatol. 2014;61:850–8.CrossRefPubMed
13.
14.
15.
He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nature Rev Genet. 2004;5:522–31.CrossRefPubMed
16.
Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics. 2013;14:319.CrossRefPubMedPubMedCentral
17.
Chen SJ, Chen GH, Chen YH, Liu CY, Chang KP, Chang YS, et al. Characterization of Epstein-Barr virus miRNAome in nasopharyngeal carcinoma by deep sequencing. PLoS ONE. 2010;5, e12745.CrossRefPubMedPubMedCentral
18.
Wittmann J, Jäck HM. Serum microRNAs as powerful cancer biomarkers. Biochim Biophys Acta. 2010;1806:200–7.PubMed
19.
Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.CrossRefPubMed
20.
Pu XX, Huang GL, Guo HQ, Guo CC, Li H, Ye S, et al. Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J Gastroenterol Hepatol. 2010;25:1674–80.CrossRefPubMed
21.
Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112:55–9.CrossRefPubMed
22.
Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. In: World Health Organization Classification of Tumors. Lyon: IARC press; 2000.
23.
Plieskatt JL, Rinaldi G, Feng Y, Levine PH, Easley S, Martinez E, et al. Methods and matrices: approaches to identifying miRNAs for Nasopharyngeal carcinoma. J Transl Med. 2014;12:3.CrossRefPubMedPubMedCentral
24.
Friedländer MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, et al. Discovering microRNAs from deep sequencing data using miRDeep. Nat Biotechnol. 2008;26:407–15.CrossRefPubMed
25.
Wang WC, Lin FM, Chang WC, Lin KY, Huang HD, Lin NS. miRExpress: analyzing high-throughput sequencing data for profiling microRNA expression. BMC Bioinformatics. 2009;10:328.CrossRefPubMedPubMedCentral
26.
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39:D152–7.CrossRefPubMed
27.
Robinson MD, McCarthy DJ, Smyth GK. EdgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139–40.CrossRefPubMed
28.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMed
29.
Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13:1668–74.CrossRefPubMedPubMedCentral
30.
Jung M, Schaefer A, Steiner I, Kempkensteffen C, Stephan C, Erbersdobler A, et al. Robust microRNA stability in degraded RNA preparations from human tissue and cell samples. Clin Chem. 2010;56:998–1006.CrossRefPubMed
31.
32.
Plieskatt, JL, Feng, Y, Rinaldi, G, Mulvenna, JP, Bethony, JM, Brindley, PJ: Circumventing qPCR inhibition to amplify miRNAs in plasma. Biomark Res. 2014. In press
33.
Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, et al. Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA. 2010;16:991–1006.CrossRefPubMedPubMedCentral
34.
Guo L, Zhao Y, Yang S, Cai M, Wu Q, Chen F. Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer. Mol Biol Rep. 2013;40:2175–86.CrossRefPubMed
35.
Torres A, Torres K, Pesci A, Ceccaroni M, Paszkowski T, Cassandrini P, et al. Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma. BMC Cancer. 2012;12:369.CrossRefPubMedPubMedCentral
36.
Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS ONE. 2009;4, e5532.CrossRefPubMedPubMedCentral
37.
Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2009;104:476–87.CrossRefPubMedPubMedCentral
38.
Kin K, Miyagawa S, Fukushima S, Shirakawa Y, Torikai K, Shimamura K, et al. Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm. J Am Heart Assoc. 2012;1:e000745.CrossRefPubMedPubMedCentral
39.
Ohyashiki K, Umezu T, Yoshizawa S, Ito Y, Ohyashiki M, Kawashima H, et al. Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin’s lymphoma. PLoS ONE. 2011;6:e16408.CrossRefPubMedPubMedCentral
40.
Braconi C, Patel T. MicroRNA expression profiling: a molecular tool for defining the phenotype of hepatocellular tumors. Hepatology. 2008;47:1807–9.CrossRefPubMed
41.
Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537–45.CrossRefPubMed
42.
Koontongkaew S. The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas. J Cancer. 2013;4:66–83.CrossRefPubMedPubMedCentral
43.
Su Y, Li X, Ji W, Sun B, Xu C, Li Z, et al. Small molecule with big role: MicroRNAs in cancer metastatic microenvironments. Cancer Lett. 2013;344:147–56.CrossRefPubMed
44.
Bronisz A, Wang Y, Nowicki MO, Peruzzi P, Ansari K, Ogawa D, et al. Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Cancer Res. 2013;74:738–50.CrossRefPubMedPubMedCentral
45.
Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, et al. Hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer. 2010;116:2148–58.PubMed
46.
Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, et al. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Molecular cell. 2009;35:856–67.CrossRefPubMedPubMedCentral
47.
Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, et al. Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol. 2010;3:109.CrossRefPubMedPubMedCentral
48.
Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288:10849–59.CrossRefPubMedPubMedCentral
49.
Tadokoro H, Umezu T, Ohyashiki K, Hirano T, Ohyashiki JH. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J Biol Chem. 2013;288:34343–51.CrossRefPubMedPubMedCentral
50.
Meng F, Henson R, Wehbe-Janek H, Smith H, Ueno Y, Patel T. The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes. J Biol Chem. 2007;282:8256–64.CrossRefPubMed
51.
Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006;130:2113–29.CrossRefPubMed
52.
53.
He Q, Cai L, Shuai L, Li D, Wang C, Liu Y, et al. Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21. Mol Carcinog. 2013;52:286–96.CrossRefPubMed
54.
Selaru FM, Olaru AV, Kan T, David S, Cheng Y, Mori Y, et al. MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology. 2009;49:1595–601.CrossRefPubMedPubMedCentral
55.
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
56.
57.
Yang R, Chen Y, Tang C, Li H, Wang B, Yan Q, et al. MicroRNA-144 suppresses cholangiocarcinoma cell proliferation and invasion through targeting platelet activating factor acetylhydrolase isoform 1b. BMC Cancer. 2014;14:917.CrossRefPubMedPubMedCentral
58.
Hu C, Huang F, Deng G, Nie W, Huang W, Zeng X. miR-31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Exp Ther Med. 2013;6:1265–70.PubMedPubMedCentral
59.
Yang H, Li TW, Peng J, Tang X, Ko KS, Xia M, et al. A mouse model of cholestasis-associated cholangiocarcinoma and transcription factors involved in progression. Gastroenterology. 2011;141:378–88.CrossRefPubMedPubMedCentral
60.
Zhong XY, Yu JH, Zhang WG, Wang ZD, Dong Q, Tai S, et al. MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression. Gene. 2012;493:44–51.CrossRefPubMed
61.
62.
Okamoto K, Miyoshi K, Murawaki Y. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells. PLoS ONE. 2013;8:e77623.CrossRefPubMedPubMedCentral
63.
Zeng B, Li Z, Chen R, Guo N, Zhou J, Zhou Q, et al. Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 2012;586:3271–8.CrossRefPubMed
64.
Wang Q, Tang H, Yin S, Dong C. Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep. 2013;29:2046–52.PubMed
65.
Braconi C, Huang N, Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology. 2010;51:881–90.PubMedPubMedCentral
66.
Peng F, Jiang J, Yu Y, Tian R, Guo X, Li X, et al. Direct targeting of SUZ12/ROCK2 by miR-200b/c inhibits cholangiocarcinoma tumourigenesis and metastasis. Br J Cancer. 2013;109:3092–104.CrossRefPubMedPubMedCentral
67.
Qiu YH, Wei YP, Shen NJ, Wang ZC, Kan T, Yu WL, et al. miR-204 inhibits epithelial to mesenchymal transition by targeting slug in intrahepatic cholangiocarcinoma cells. Cell Physiol Biochem. 2013;32:1331–41.CrossRefPubMed
68.
Chen L, Yan HX, Yang W, Hu L, Yu LX, Liu Q, et al. The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma. J Hepatol. 2009;50:358–69.CrossRefPubMed
69.
Li B, Han Q, Zhu Y, Yu Y, Wang J, Jiang X. Down-regulation of miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist. FEBS J. 2012;279:2393–8.CrossRefPubMed
70.
Meng F, Wehbe-Janek H, Henson R, Smith H, Patel T. Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes. Oncogene. 2008;27:378–86.CrossRefPubMed
71.
Chen Y, Luo J, Tian R, Sun H, Zou S. miR-373 negatively regulates methyl-CpG-binding domain protein 2 (MBD2) in hilar cholangiocarcinoma. Dig Dis Sci. 2011;56:1693–701.CrossRefPubMed
72.
Iwaki J, Kikuchi K, Mizuguchi Y, Kawahigashi Y, Yoshida H, Uchida E, et al. MiR-376c down-regulation accelerates EGF-dependent migration by targeting GRB2 in the HuCCT1 human intrahepatic cholangiocarcinoma cell line. PLoS ONE. 2013;8, e69496.CrossRefPubMedPubMedCentral
73.
Olaru AV, Ghiaur G, Yamanaka S, Luvsanjav D, An F, Popescu I, et al. MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint. Hepatology. 2011;54:2089–98.CrossRefPubMedPubMedCentral
Metadata
Title
A microRNA profile associated with Opisthorchis viverrini-induced cholangiocarcinoma in tissue and plasma
Authors
Jordan Plieskatt
Gabriel Rinaldi
Yanjun Feng
Jin Peng
Samantha Easley
Xinying Jia
Jeremy Potriquet
Chawalit Pairojkul
Vajarabhongsa Bhudhisawasdi
Banchob Sripa
Paul J Brindley
Jeffrey Bethony
Jason Mulvenna
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1270-5

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