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Current Genomics

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ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

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General Research Article

Exosomal miR-1298 and lncRNA-RP11-583F2.2 Expression in Hepatocellular Carcinoma

Author(s): Marwa Matboli*, Mariam E. Labib, Hanaa El-Tayeb Nasser, Ahmed H.F. El-Tawdi, Eman K. Habib and Randa Ali-Labib

Volume 21, Issue 1, 2020

Page: [46 - 55] Pages: 10

DOI: 10.2174/1389202920666191210111849

Price: $65

Abstract

Aim: The aim of this study was to explore the expression of exosomal non-coding RNAs (ncRNAs) in the sera of patients with HCC versus control.

Methods: Firstly, Bioinformatics analysis was conducted to retrieve ncRNAs specific to HCC (hsamiRNA- 1298 and lncRNA-RP11-583F2.2). Afterwards, extraction and characterization of exosomes were performed. We measured the expression of the chosen exosomal RNAs by reverse transcriptase quantitative real-time PCR in sera of 60 patients with HCC, 42 patients with chronic hepatitis C (CHC) infection and 18 healthy normal volunteers.

Results: The exosomal ncRNAs [hsa-miRNA-1298, lncRNA-RP11-583F2.2] had better sensitivity and specificity than alpha-fetoprotein (AFP) in HCC diagnosis.

Conclusion: The exosomal hsa-miRNA-1298, lncRNA-RP11-583F2.2 can be potential biomarkers for HCC diagnosis.

Keywords: Hepatocellular carcinoma, exosome, miRNA, lncRNA, diagnosis, chronic hepatitis C.

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[1]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Cancer facts and figures Atlanta;American Cancer Society: Atlanta, GA, 2019; 1-71.
[3]
National Cancer Registry Program of Egypt Magnitude of hepatocellular carcinoma in Egypt, 2011.
[4]
Elghazaly, H.; Gaballah, A.; Bahie Eldin, N. Clinic-pathological pattern of hepatocellular carcinoma (HCC) in Egypt. Ann. Oncol., 2018, 29(5), v5-v6.
[http://dx.doi.org/10.1093/annonc/mdy151.018]
[5]
Amer, N.A.; Gemaay, M.A.; Mohamed, A.E.; Hussein, M.M.; Shehad, I. Prevalence of viral hepatitis in Egyptian patients with hepatocellular carcinoma. Egyptian Liver J., 2013, 3(1), 6-9.
[http://dx.doi.org/10.1097/01.ELX.0000424247.25858.79]
[6]
Papandreou, I.; Lim, A.L.; Laderoute, K.; Denko, N.C. Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death Differ., 2008, 15(10), 1572-1581.
[http://dx.doi.org/10.1038/cdd.2008.84] [PMID: 18551130]
[7]
Jin, S.; White, E. Tumor suppression by autophagy through the management of metabolic stress. Autophagy, 2008, 4, 563-566.
[http://dx.doi.org/10.4161/auto.5830]
[8]
Christianson, H.C.; Svensson, K.J.; van Kuppevelt, T.H.; Li, J.P.; Belting, M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc. Natl. Acad. Sci. USA, 2013, 110(43), 17380-17385.
[http://dx.doi.org/10.1073/pnas.1304266110] [PMID: 24101524]
[9]
Gajos-Michniewicz, A.; Duechler, M.; Czyz, M. MiRNA in melanoma-derived exosomes. Cancer Lett., 2014, 347(1), 29-37.
[http://dx.doi.org/10.1016/j.canlet.2014.02.004] [PMID: 24513178]
[10]
Stoorvogel, W.; Kleijmeer, M.J.; Geuze, H.J.; Raposo, G. The biogenesis and functions of exosomes. Traffic, 2002, 3, 321-330.
[http://dx.doi.org/10.1034/j.1600-0854.2002.30502.x]
[11]
Pant, S.; Hilton, H.; Burczynski, M.E. The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem. Pharmacol., 2012, 83(11), 1484-1494.
[http://dx.doi.org/10.1016/j.bcp.2011.12.037] [PMID: 22230477]
[12]
Sohn, W.; Kim, J.; Kang, S.H.; Yang, S.R.; Cho, J-Y.; Cho, H.C.; Shim, S.G.; Paik, Y-H. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp. Mol. Med., 2015, 47e184
[http://dx.doi.org/10.1038/emm.2015.68] [PMID: 26380927]
[13]
Takahashi, K.; Yan, I.K.; Kogure, T.; Haga, H.; Patel, T. Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio, 2014, 4, 458-467.
[http://dx.doi.org/10.1016/j.fob.2014.04.007] [PMID: 24918061]
[14]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[15]
Amal, S.I.; Hussein, M.K.; Nabiel, N.H.; Hoda, B.; Hossam, K. Cancer incidence in Egypt: results of the national population- based cancer registry program. J. Cancer Epidemiol., 2014, 437971, 18.
[http://dx.doi.org/10.1155/2014/437971]
[16]
Nair, M.; Sandhu, S.S.; Sharma, A.K. Prognostic and predictive biomarkers in cancer. Curr. Cancer Drug Targets, 2014, 14(5), 477-504.
[http://dx.doi.org/10.2174/1568009614666140506111118] [PMID: 24807144]
[17]
Azmi, A.S.; Bao, B.; Sarkar, F.H. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev., 2013, 32(3-4), 623-642.
[http://dx.doi.org/10.1007/s10555-013-9441-9] [PMID: 23709120]
[18]
Kogure, T.; Lin, W-L.; Yan, I.K.; Braconi, C.; Patel, T. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology, 2011, 54(4), 1237-1248.
[http://dx.doi.org/10.1002/hep.24504] [PMID: 21721029]
[19]
Ji, H.; Greening, D.W.; Barnes, T.W.; Lim, J.W.; Tauro, B.J.; Rai, A.; Xu, R.; Adda, C.; Mathivanan, S.; Zhao, W.; Xue, Y.; Xu, T.; Zhu, H.J.; Simpson, R.J. Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics, 2013, 13(10-11), 1672-1686.
[http://dx.doi.org/10.1002/pmic.201200562] [PMID: 23585443]
[20]
Laura, S.; Cecilia, B.; Claudia, M.; Franca, C.; Raffaele, S.; Carla, C. Functional roles and therapeutic applications of exosomes in hepatocellular carcinoma. BioMed Res. Int., 2017, 2017, 1-8.
[http://dx.doi.org/10.1155/2017/2931813]
[21]
He, M.; Qin, H.; Poon, T.C.; Sze, S-C.; Ding, X.; Co, N.N.; Ngai, S-M.; Chan, T-F.; Wong, N. Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs. Carcinogenesis, 2015, 36(9), 1008-1018.
[http://dx.doi.org/10.1093/carcin/bgv081] [PMID: 26054723]
[22]
Yuyama, K.; Sun, H.; Mitsutake, S.; Igarashi, Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J. Biol. Chem., 2012, 287(14), 10977-10989.
[http://dx.doi.org/10.1074/jbc.M111.324616] [PMID: 22303002]
[23]
Melo, S.A.; Luecke, L.B.; Kahlert, C.; Fernandez, A.F.; Gammon, S.T.; Kaye, J.; LeBleu, V.S.; Mittendorf, E.A.; Weitz, J.; Rahbari, N.; Reissfelder, C.; Pilarsky, C.; Fraga, M.F.; Piwnica-Worms, D.; Kalluri, R. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature, 2015, 523(7559), 177-182.
[http://dx.doi.org/10.1038/nature14581] [PMID: 26106858]
[24]
Avgeris, M.; Panoutsopoulou, K.; Papadimitriou, M.A.; Scorilas, A. Circulating exosomal miRNAs: clinical significance in human cancers. Expert Rev. Mol. Diagn., 2019, 19(11), 979-995.
[http://dx.doi.org/10.1080/14737159.2019.1673732] [PMID: 31594418]
[25]
Alegre, E.; Zubiri, L.; Perez-Gracia, J.L.; González-Cao, M.; Soria, L.; Martín-Algarra, S.; González, A. Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin. Chim. Acta, 2016, 454, 28-32.
[http://dx.doi.org/10.1016/j.cca.2015.12.031] [PMID: 26724367]
[26]
Suchorska, W.M.; Lach, M.S. The role of exosomes in tumor progression and metastasis.(Review) Oncol. Rep., 2016, 35(3), 1237-1244.
[http://dx.doi.org/10.3892/or.2015.4507] [PMID: 26707854 ]
[27]
Fornari, F.; Ferracin, M.; Trerè, D.; Milazzo, M.; Marinelli, S.; Galassi, M.; Venerandi, L.; Pollutri, D.; Patrizi, C.; Borghi, A.; Foschi, F.G.; Stefanini, G.F.; Negrini, M.; Bolondi, L.; Gramantieri, L. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, identify cirrhotic patients with HCC. PLoS One, 2015, 10(10)e0141448
[http://dx.doi.org/10.1371/journal.pone.0141448] [PMID: 26509672]
[28]
Sugimachi, K.; Matsumura, T.; Hirata, H.; Uchi, R.; Ueda, M.; Ueo, H.; Shinden, Y.; Iguchi, T.; Eguchi, H.; Shirabe, K.; Ochiya, T.; Maehara, Y.; Mimori, K. Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br. J. Cancer, 2015, 112(3), 532-538.
[http://dx.doi.org/10.1038/bjc.2014.621] [PMID: 25584485]
[29]
Kogure, T.; Yan, I.K.; Lin, W-L.; Patel, T. Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer, 2013, 4(7-8), 261-272.
[http://dx.doi.org/10.1177/1947601913499020] [PMID: 24167654 ]
[30]
Liu, W-H.; Ren, L-N.; Wang, X.; Wang, T.; Zhang, N.; Gao, Y.; Luo, H.; Navarro-Alvarez, N.; Tang, L.J. Combination of exosomes and circulating microRNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J. Cancer Res. Clin. Oncol., 2015, 141(10), 1767-1778.
[http://dx.doi.org/10.1007/s00432-015-1943-0] [PMID: 25724413 ]
[31]
Wei, J-X.; Lv, L-H.; Wan, Y.L.; Cao, Y.; Li, G.L.; Lin, H-M.; Zhou, R.; Shang, C-Z.; Cao, J.; He, H.; Han, Q-F.; Liu, P-Q.; Zhou, G.; Min, J. Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells. Hepatology, 2015, 61(4), 1284-1294.
[http://dx.doi.org/10.1002/hep.27660] [PMID: 25503676]
[32]
Zhou, Y.; Dang, J.; Chang, K.Y.; Yau, E.; Aza-Blanc, P.; Moscat, J.; Rana, T.M. miR-1298 inhibits mutant KRAS-driven tumor growth by repressing FAK and LAMB3. Cancer Res., 2016, 76(19), 5777-5787.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2936] [PMID: 27698189 ]
[33]
Fornari, F.; Pollutri, D.; Patrizi, C.; La Bella, T.; Marinelli, S.; Casadei Gardini, A.; Marisi, G.; Baron Toaldo, M.; Baglioni, M.; Salvatore, V.; Callegari, E.; Baldassarre, M.; Galassi, M.; Giovannini, C.; Cescon, M.; Ravaioli, M.; Negrini, M.; Bolondi, L.; Gramantieri, L. In hepatocellular carcinoma miR-221 modulates sorafenib resistance through inhibition of caspase-3-mediated apoptosis. Clin. Cancer Res., 2017, 23(14), 3953-3965.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-1464] [PMID: 28096271]
[34]
Liu, C.; Cao, B.; Liu, N.; Zhou, Z.; Yang, G.; Zhou, P. Increased expression of long noncoding RNA RP11-62F24.2 in gastric cancer and its clinical significance. Clin. Lab., 2017, 63(9), 1475-1479.
[http://dx.doi.org/10.7754/Clin.Lab.2017.170334] [PMID: 28879717]
[35]
Sun, J.; Song, Y.; Chen, X.; Zhao, J.; Gao, P.; Huang, X.; Xu, H.; Wang, Z. Novel long non-coding RNA RP11-119F7.4 as a potential biomarker for the development and progression of gastric cancer. Oncol. Lett., 2015, 10(1), 115-120.
[http://dx.doi.org/10.3892/ol.2015.3186] [PMID: 26170986]
[36]
Abd, E.L.; Gwad, A.; Matboli, M.; El-Tawdi, A.; Habib, E.K.; Shehata, H.; Ibrahim, D.; Tash, F. Role of exosomal competing endogenous RNA in patients with hepatocellular carcinoma. J. Cell. Biochem., 2018, 119(10), 8600-8610.
[http://dx.doi.org/10.1002/jcb.27109] [PMID: 30015383]

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