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Research Article

Transcriptomic Analysis of the Aquaporin Gene Family and Associated Interactors in Rectal Cancer

Author(s): Dimitrios E. Magouliotis, Vasiliki S. Tasiopoulou, Ioannis Baloyiannis, Ioannis Mamaloudis and George Tzovaras*

Volume 9, Issue 2, 2020

Page: [153 - 166] Pages: 14

DOI: 10.2174/2211536608666190917153332

Abstract

Background: Rectal Cancer (RC) is a common type of cancer with poor prognosis. The identification of biomarkers regarding RC diagnosis, monitoring, and prognosis is crucial.

Objectives: The purpose of the present study was to evaluate the differential expression of the Aquaporin (AQP) gene family network in RC, and the effect of Radiotherapy (RT) on their expression profile, to indicate novel biomarkers and prognostic factors.

Methods: We used data mining techniques to construct the network of the AQP-associated genes to determine the Differentially Expressed Genes (DEGs) in RC and in irradiated as compared to nonirradiated RC patients. Furthermore, survival data of The Cancer Genome Atlas (TCGA) were analysed to assess the prognostic role of the DEGs, along with the functional enrichment of gene ontologies and miRNAs related to the DEGs in RC.

Results: Microarray data of one PubMed GEO dataset was extracted, incorporating 22 RC and 20 normal rectal tissue samples. Eight DEGs were reported. Four DEGs were up-regulated and four downregulated in RC. Correlations were identified among the DEGs. Deming regression analysis was performed in order to demonstrate the equations describing these correlations. One gene (Aquaporin 3) was downregulated in irradiated RC samples compared with non-irradiated samples. The most significantly affected biological pathways and miRNAs were identified by functional enrichment analysis.

Conclusion: The present study demonstrates an eight-gene molecular panel that could facilitate as biomarkers regarding RC patients, which are potential targets of five miRNA families. Finally, our results highlight the effect of radiotherapy on AQPs and the associated pathways in RC.

Keywords: AQP3, aquaporin, biomarker, in silico, miRNA, radiotherapy, rectal cancer, transcriptomics.

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[1]
Torre LA, Bray F, Siegel RL, 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]
Cereda M, Gambardella G, Benedetti L, et al. Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes. Nat Commun 2016; 7: 12072.
[http://dx.doi.org/10.1038/ncomms12072] [PMID: 27377421]
[3]
Jo YM, Park TI, Lee HY, Jeong JY, Lee WK. Prognostic significance of aquaporin 5 expression in non-small cell lung cancer. J Pathol Transl Med 2016; 50(2): 122-8.
[http://dx.doi.org/10.4132/jptm.2015.10.31] [PMID: 26863575]
[4]
Rogler G. Chronic ulcerative colitis and colorectal cancer. Cancer Lett 2014; 345(2): 235-41.
[http://dx.doi.org/10.1016/j.canlet.2013.07.032] [PMID: 23941831]
[5]
Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet 2014; 383(9927): 1490-502.
[http://dx.doi.org/10.1016/S0140-6736(13)61649-9] [PMID: 24225001]
[6]
Videira M, Reis RL, Brito MA. Deconstructing breast cancer cell biology and the mechanisms of multidrug resistance. Biochim Biophys Acta 2014; 1846(2): 312-25.
[PMID: 25080053]
[7]
Nagaraju GP, Basha R, Rajitha B, et al. Aquaporins: their role in gastrointestinal malignancies. Cancer Lett 2016; 373(1): 12-8.
[http://dx.doi.org/10.1016/j.canlet.2016.01.003] [PMID: 26780474]
[8]
Verkman AS, Hara-Chikuma M, Papadopoulos MC. Aquaporins--new players in cancer biology. J Mol Med (Berl) 2008; 86(5): 523-9.
[http://dx.doi.org/10.1007/s00109-008-0303-9] [PMID: 18311471]
[9]
Papadopoulos MC, Saadoun S. Key roles of aquaporins in tumor biology. Biochim Biophys Acta 2015; 1848(10 Pt B): 2576-83.
[http://dx.doi.org/10.1016/j.bbamem.2014.09.001] [PMID: 25204262]
[10]
Delporte C. Aquaporins in salivary glands and pancreas. Biochim Biophys Acta 2014; 1840(5): 1524-32.
[http://dx.doi.org/10.1016/j.bbagen.2013.08.007] [PMID: 23954206]
[11]
Burghardt B, Elkaer ML, Kwon TH, et al. Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas. Gut 2003; 52(7): 1008-16.
[http://dx.doi.org/10.1136/gut.52.7.1008] [PMID: 12801959]
[12]
Niu D, Kondo T, Nakazawa T, et al. Expression of aquaporin3 in human neoplastic tissues. Histopathology 2012; 61(4): 543-51.
[http://dx.doi.org/10.1111/j.1365-2559.2011.04165.x] [PMID: 22882482]
[13]
Direito I, Paulino J, Vigia E, Brito MA, Soveral G. Differential expression of aquaporin-3 and aquaporin-5 in pancreatic ductal adenocarcinoma. J Surg Oncol 2017; 115(8): 980-96.
[http://dx.doi.org/10.1002/jso.24605] [PMID: 28471475]
[14]
Kamburov A, Stelzl U, Lehrach H, Herwig R. The consensusPathDB interaction database: 2013 update. Nucleic Acids Res 2013; 41(Database issue): D793-800.
[http://dx.doi.org/10.1093/nar/gks1055] [PMID: 23143270]
[15]
Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 2010; 38(Web Server issue): W214-20.
[http://dx.doi.org/10.1093/nar/gkq537] [PMID: 20576703]
[16]
Chen J, Bardes EE, Aronow BJ, Jegga AG. Topp gene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 2009; 37(Web Server issue): W305-11.
[http://dx.doi.org/10.1093/nar/gkp427] [PMID: 19465376]
[17]
Goswami CP, Nakshatri H. PROGgene: gene expression based survival analysis web application for multiple cancers. J Clin Bioinform 2013; 3(1): 22.
[http://dx.doi.org/10.1186/2043-9113-3-22] [PMID: 24165311]
[18]
Ikeda M, Beitz E, Kozono D, Guggino WB, Agre P, Yasui M. Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem 2002; 277(42): 39873-9.
[http://dx.doi.org/10.1074/jbc.M207008200] [PMID: 12177001]
[19]
Rubenwolf PC, Otto W, Denzinger S, Hofstädter F, Wieland W, Georgopoulos NT. Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage. World J Urol 2014; 32(4): 991-7.
[http://dx.doi.org/10.1007/s00345-013-1153-9] [PMID: 24022233]
[20]
Chen XF, Li CF, Lü L, Mei ZC. Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma. Mol Med Rep 2016; 13(6): 5283-9.
[http://dx.doi.org/10.3892/mmr.2016.5184] [PMID: 27121567]
[21]
Viggiano L, Rocchi M, Svelto M, Calamita G. Assignment of the Aquaporin-8 water channel gene (AQP8) to human chromosome 16p12. Cytogenet Cell Genet 1999; 84(3-4): 208-10.
[http://dx.doi.org/10.1159/000015260] [PMID: 10393433]
[22]
Wu Q, Yang ZF, Wang KJ, et al. AQP8 inhibits colorectal cancer growth and metastasis by down-regulating PI3K/AKT signaling and PCDH7 expression. Am J Cancer Res 2018; 1;8(2): 266-79.
[23]
Wang W, Li Q, Yang T, et al. Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance. World J Surg Oncol 2012; 10: 242.
[http://dx.doi.org/10.1186/1477-7819-10-242] [PMID: 23148732]
[24]
Tsukaguchi H, Weremowicz S, Morton CC, Hediger MA. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol 1999; 277(5): F685-96.
[PMID: 10564231]
[25]
Ishibashi K, Kuwahara M, Gu Y, Tanaka Y, Marumo F, Sasaki S. Cloning and functional expression of a new Aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol. Biochem Biophys Res Commun 1998; 244(1): 268-74.
[http://dx.doi.org/10.1006/bbrc.1998.8252] [PMID: 9514918]
[26]
Huang D, Feng X, Liu Y, et al. AQP9-induced cell cycle arrest is associated with RAS activation and improves chemotherapy treatment efficacy in colorectal cancer. Cell Death Dis 2017; 8(6) e2894
[http://dx.doi.org/10.1038/cddis.2017.282] [PMID: 28640255]
[27]
Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett 2007; 250(1): 36-46.
[http://dx.doi.org/10.1016/j.canlet.2006.09.013] [PMID: 17084522]
[28]
Tsukaguchi H, Shayakul C, Berger UV, et al. Molecular characterization of a broad selectivity neutral solute channel. J Biol Chem 1998; 273(38): 24737-43.
[http://dx.doi.org/10.1074/jbc.273.38.24737] [PMID: 9733774]
[29]
Wu B, Beitz E. Aquaporins with selectivity for unconventional permeants. Cell Mol Life Sci 2007; 64(18): 2413-21.
[http://dx.doi.org/10.1007/s00018-007-7163-2] [PMID: 17571212]
[30]
Verkman AS. Aquaporins in clinical medicine. Annu Rev Med 2012; 63: 303-16.
[http://dx.doi.org/10.1146/annurev-med-043010-193843] [PMID: 22248325]
[31]
Li A, Lu D, Zhang Y, et al. Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance. Oncol Rep 2013; 29(2): 535-40.
[http://dx.doi.org/10.3892/or.2012.2144] [PMID: 23165320]
[32]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[33]
To KK, Tong CW, Wu M, Cho WC. MicroRNAs in the prognosis and therapy of colorectal cancer: from bench to bedside. World J Gastroenterol 2018; 24(27): 2949-73.
[http://dx.doi.org/10.3748/wjg.v24.i27.2949] [PMID: 30038463]
[34]
Masuda T, Hayashi N, Kuroda Y, Ito S, Eguchi H, Mimori K. MicroRNAs as biomarkers in colorectal cancer. Cancers (Basel) 2017; 9(9): 124.
[http://dx.doi.org/10.3390/cancers9090124] [PMID: 28902152]
[35]
Zhang Z, Han Y, Sun G, Liu X, Jia X, Yu X. MicroRNA-325-3p inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma by down-regulation of aquaporin 5. Cell Mol Biol Lett 2019; 13(12): 24.
[http://dx.doi.org/10.1186/s11658-019-0137-1]
[36]
Lin T, Zhou S, Gao H, Li Y, Sun L. MicroRNA-325 is a potential biomarker and tumor regulator in human bladder cancer. Technol Cancer Res Treat 2018; 17 1533033818790536
[http://dx.doi.org/10.1177/1533033818790536] [PMID: 30176759]
[37]
Ma J, Zhu Y, Wang Z, et al. miR-593 inhibits proliferation of colon cancer cells in vitro by down-regulating PLK1. Nan Fang Yi Ke Da Xue Xue Bao 2019; 39(2): 144-9.
[http://dx.doi.org/10.12122/j.issn.1673-4254.2019.09.03] [PMID: 30890500]
[38]
Wang X, Wu X. The role of microRNA-1207-5p in colorectal cancer. Clin Lab 2017; 63(11): 1875-82.
[http://dx.doi.org/10.7754/Clin.Lab.2017.170625] [PMID: 29226644]
[39]
Tian H, Wang X, Lu J, Tian W, Chen P. MicroRNA-621 inhibits cell proliferation and metastasis in bladder cancer by suppressing Wnt/β-catenin signaling. Chem Biol Interact 2019; 308: 244-51.
[http://dx.doi.org/10.1016/j.cbi.2019.05.042] [PMID: 31145890]

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