mir-1792 Expression In Various Stages Of Chronic Hepatitis C Viral (HCV) Infection: Correlation With PEG-10 And PTEN
[Full Text]
AUTHOR(S)
Heba M Zamil, Alshimaa M Elmalawany, Yasser BM Ali, Ahmed A. El-Shaarawy, Roba M Talaat
KEYWORDS
miR-17-92; HCC; PEG10; PTEN; Cirrhosis; HCV
ABSTRACT
Background: Circulating microRNAs (miRNAs) have been reported as a promising epigenetic biomarker. miRNAs have significant diagnostic potential for hepatocellular carcinoma (HCC). In this study, expression of miR-17-92 in Hepatitis (C)-related Liver Cirrhosis and HCC was evaluated. miR-17-92 expression was assessed using quantitative real-time Polymerase chain reaction (RT-PCR) in 145plasma samples [45 healthy controls, 25 HCC patients, and 75 cirrhotic patients with various Child-Pugh stages]. The relation between miR-17-92 and paternally expressed 10 (PEG10) and Phosphatase and tensin homolog (PTEN) proteins were investigated. Results: Our study found a significant reduction in miR-17-92 expression (P<0.001) in HCV-infected patients [either cirrhotic or HCC patients] when compared with the healthy control group. miR-17-92 expression levels with a cutoff value of 1.175-fold change had a 64% sensitivity and 34.9% specificity. With a cutoff value of 8.5 ng/ ml, alpha-fetoprotein (AFP) had a high sensitivity (87.5%) and specificity (100%) in the detection of HCC. BothPEG10 (P<0.001) and PTEN (P<0.01) were significantly decreased in HCC patients as compared with the healthy controls. The detection of miR-17-92, PEG10, and PTEN is valuable in elucidating the complex regulatory mechanisms governing HCC tumorigenesis. Conclusions: The combined detection of these factors may have clinical importance in prognostic, diagnosis, judgment, and therapeutic options for primary HCC.A future prospective large-scale study is recommended to support our findings and prove the mechanistic connections between miR-17-92 and PEG10/PTEN levels and HCV disease manifestations.
REFERENCES
[1]. Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development. 2005 Nov;132(21):4653-62. DOI: 10.1242/dev.02073. PMID: 16224045.
[2]. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. PMID: 14744438.
[3]. Baure J. D. Creatinine method using picric acid in the clinical laboratory. Clinical Lab Methods. 9th ed. Saint Louis USA: Mosby CV Company. 1982; P. 495-956
[4]. Campanero MR, Flemington EK. Regulation of E2F through ubiquitin-proteasome-dependent degradation: stabilization by the pRB tumor suppressor protein. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2221-6. DOI: 10.1073/pnas.94.6.2221. PMID: 9122175; PMCID: PMC20068.
[5]. Cardin R, Piciocchi M, Sinigaglia A, Lavezzo E, Bortolami M, Kotsafti A, Cillo U, Zanus G, Mescoli C, Rugge M, Farinati F. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma. BMC Cancer. 2012 May 15;12:177. DOI: 10.1186/1471-2407-12-177. Erratum in: BMC Cancer. 2014;14:284. Multiple author names corrected. PMID: 22587342; PMCID: PMC3420318.
[6]. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. DOI: 10.3322/caac.21338. Epub 2016 Jan 25. PMID: 26808342.
[7]. Conv N.V. Donev I.S. Konsoulova-Kirova A.A. Chervenkov T.G. Kashlov J.K. and Ivanov KD. Serum expression levels of miR-17, miR-21, and miR-92 as potential biomarkers for recurrence after adjuvant chemotherapy in colon cancer patients. Biosci Trends. 2015; 9[6]:393-401.
[8]. Dakhlallah D, Batte K, Wang Y, Cantemir-Stone CZ, Yan P, Nuovo G, Mikhail A, Hitchcock CL, Wright VP, Nana-Sinkam SP, Piper MG, Marsh CB. Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med. 2013 Feb 15;187(4):397-405. DOI: 10.1164/rccm.201205-0888OC. Epub 2013 Jan 10. PMID: 23306545; PMCID: PMC3603596.
[9]. Doumas BT, Kwok-Cheung PP, Perry BW, Jendrzejczak B, McComb RB, Schaffer R, Hause LL. Candidate reference method for determination of total bilirubin in serum: development and validation. Clin Chem. 1985 Nov;31(11):1779-89. PMID: 4053346.
[10]. Duyu M, Durmaz B, Gunduz C, Vergin C, Yilmaz Karapinar D, Aksoylar S, Kavakli K, Cetingul N, Irken G, Yaman Y, Ozkinay F, Cogulu O. Prospective evaluation of whole genome microRNA expression profiling in childhood acute lymphoblastic leukemia. Biomed Res Int. 2014;2014:967585. DOI: 10.1155/2014/967585. Epub 2014 May 14. PMID: 24955371; PMCID: PMC4053274.
[11]. Ernst A, Hofmann S, Ahmadi R, Becker N, Korshunov A, Engel F, Hartmann C, Felsberg J, Sabel M, Peterziel H, Durchdewald M, Hess J, Barbus S, Campos B, Starzinski-Powitz A, Unterberg A, Reifenberger G, Lichter P, Herold-Mende C, Radlwimmer B. Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumor-relevant genes associated with survival. Clin Cancer Res. 2009 Nov 1;15(21):6541-50. DOI: 10.1158/1078-0432.CCR-09-0695. Epub 2009 Oct 27. PMID: 19861460.
[12]. Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013 Feb;57(2):840-7. DOI: 10.1002/hep.26095. Epub 2012 Dec 26. PMID: 23081718.
[13]. Gruszka R, Zakrzewska M. The Oncogenic Relevance of miR-17-92 Cluster and Its Paralogous miR-106b-25 and miR-106a-363 Clusters in Brain Tumors. Int J Mol Sci. 2018 Mar 16;19(3):879. DOI: 10.3390/ijms19030879. PMID: 29547527; PMCID: PMC5877740.
[14]. Hofmann F, Martelli F, Livingston DM, Wang Z. The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway. Genes Dev. 1996 Dec 1;10(23):2949-59. DOI: 10.1101/gad.10.23.2949. PMID: 8956996.
[15]. Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW, Changchien CS, Lee CM, Tai MH. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer. 2003 Apr 15;97(8):1929-40. DOI: 10.1002/cncr.11266. PMID: 12673720.
[16]. Jacobs S. L. Henry R. J. and Segalove M. Studies on the determination of bile pigments: V. comparison of some methods for determination of total, free and conjugated bilirubin in serum. Clin Chem. 1964 May;10:433-9. PMID: 14185801.
[17]. Ji M, Rao E, Ramachandrareddy H, Shen Y, Jiang C, Chen J, Hu Y, Rizzo A, Chan WC, Fu K, McKeithan TW. Multiple mechanisms in B-cell malignancies regulate the miR-17-92 microRNA cluster. Am J Pathol. 2011 Oct;179(4):1645-56. DOI: 10.1016/j.ajpath.2011.06.008. Epub 2011 Jul 30. PMID: 21806958; PMCID: PMC3181398.
[18]. Khalid A, Hussain T, Manzoor S, Saalim M, Khaliq S. PTEN: A potential prognostic marker in virus-induced hepatocellular carcinoma. Tumour Biol. 2017 Jun;39(6):1010428317705754. DOI: 10.1177/1010428317705754. PMID: 28621226.
[19]. Kind PR, King EJ. Estimation of plasma phosphatase by determination of hydrolyzed phenol with amino-antipyrine. J Clin Pathol. 1954 Nov;7(4):322-6. DOI: 10.1136/jcp.7.4.322. PMID: 13286357; PMCID: PMC1023845.
[20]. Li CM, Margolin AA, Salas M, Memeo L, Mansukhani M, Hibshoosh H, Szabolcs M, Klinakis A, Tycko B. PEG10 is a c-MYC target gene in cancer cells. Cancer Res. 2006 Jan 15;66(2):665-72. DOI: 10.1158/0008-5472.CAN-05-1553. PMID: 16423995.
[21]. Liu, D. L., Lu, L. L., Dong, L. L., Liu, Y., Bian, X. Y., Lian, B. F., Xie, L., Wen, D., Gao, D. M., Ke, A. W., Fan, J., & Wu, W. Z. (2020). miR-17-5p and miR-20a-5p suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop. Theranostics, 10(8), 3668–3683. https://DOI.org/10.7150/thno.41365
[22]. Li L, Shi B, Chen J, Li C, Wang S, Wang Z, Zhu G. An E2F1/MiR-17-92 Negative Feedback Loop mediates proliferation of Mouse Palatal Mesenchymal Cells. Sci Rep. 2017 Jul 11;7(1):5148. DOI: 10.1038/s41598-017-05479-7. PMID: 28698574; PMCID: PMC5506009.
[23]. Li M, Guan X, Sun Y, Mi J, Shu X, Liu F, Li C. miR-92a family and their target genes in tumorigenesis and metastasis. Exp Cell Res. 2014 Apr 15;323(1):1-6. DOI: 10.1016/j.yexcr.2013.12.025. Epub 2014 Jan 4. PMID: 24394541.
[24]. Li, S., Zhang, H. Y., Du, Z. X., Li, C., An, M. X., Zong, Z. H., Liu, B. Q., & Wang, H. Q. (2016). Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells. Oncotarget, 7(43), 70364–70377. https://doi.org/10.18632/oncotarget.12217
[25]. Li X, Xiao R, Tembo K, Hao L, Xiong M, Pan S, Yang X, Yuan W, Xiong J, Zhang Q. PEG10 promotes human breast cancer cell proliferation, migration, and invasion. Int J Oncol. 2016 May;48(5):1933-42. DOI: 10.3892/ijo.2016.3406. Epub 2016 Feb 23. PMID: 26934961.
[26]. Li Y, Xu A, Jia S, Huang J. Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma. Oncol Lett. 2019 May;17(5):4222-4228. DOI: 10.3892/ol.2019.10127. Epub 2019 Mar 8. PMID: 30988804; PMCID: PMC6447942.
[27]. Liu J, Zheng M, Tang YL, Liang XH, Yang Q. MicroRNAs, an active and versatile group in cancers. Int J Oral Sci. 2011 Oct;3(4):165-75. DOI: 10.4248/IJOS11063. PMID: 22010574; PMCID: PMC3469973.
[28]. Liu M, Jiang L, Guan XY. The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update. Protein Cell. 2014 Sep;5(9):673-91. DOI: 10.1007/s13238-014-0065-9. Epub 2014 Jun 11. PMID: 24916440; PMCID: PMC4145080.
[29]. Lorini, S., Gragnani, L., & Zignego, A. L. (2020). The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis. Viruses, 12(12), 1364. https://DOI.org/10.3390/v12121364.
[30]. Malaney P, Palumbo E, Semidey-Hurtado J, Hardee J, Stanford K, Kathiriya JJ, Patel D, Tian Z, Allen-Gipson D, Davé V. PTEN Physically Interacts with and Regulates E2F1-mediated Transcription in Lung Cancer. Cell Cycle. 2018;17(8):947-962. DOI: 10.1080/15384101.2017.1388970. Epub 2018 May 31. PMID: 29108454; PMCID: PMC6103743.
[31]. Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008 Apr 18;133(2):217-22. DOI: 10.1016/j.cell.2008.04.001. PMID: 18423194; PMCID: PMC2732113.
[32]. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007 Jul 6;317(5834):121-4. DOI: 10.1126/science.1140485. Erratum in: Science. 2009 Dec 4;326(5958):1346. PMID: 17615358.
[33]. Olive V, Jiang I, He L. mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 2010 Aug;42(8):1348-54. DOI: 10.1016/j.biocel.2010.03.004. Epub 2010 Mar 19. PMID: 20227518; PMCID: PMC3681296.
[34]. Omran NM, El-Sherbini SM, Hegazy O, Elshaarawy AA, Talaat RM. Crosstalk between miR-215 and epithelial-mesenchymal transition specific markers (E-cadherin and N-cadherin) in different chronic HCV infection stages. J Med Virol. 2020 Aug;92(8):1231-1238. DOI: 10.1002/jmv.25637. Epub 2019 Dec 30. PMID: 31769519.
[35]. Ono R, Kobayashi S, Wagatsuma H, Aisaka K, Kohda T, Kaneko-Ishino T, Ishino F. A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics. 2001 Apr 15;73(2):232-7. DOI: 10.1006/geno.2001.6494. PMID: 11318613.
[36]. Peng, YP., Zhu, Y., Yin, LD. et al. PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer. J Exp Clin Cancer Res 36, 30 (2017). https://doi.org/10.1186/s13046-017-0500-x.
[37]. Petrocca F, Vecchione A, Croce CM. Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor-beta signaling. Cancer Res. 2008 Oct 15;68(20):8191-4. DOI: 10.1158/0008-5472.CAN-08-1768. PMID: 18922889.
[38]. Pickering MT, Stadler BM, Kowalik TF. miR-17 and miR-20a temper an E2F1-induced G1 checkpoint to regulate cell cycle progression. Oncogene. 2009 Jan 8;28(1):140-5. DOI: 10.1038/onc.2008.372. Epub 2008 Oct 6. PMID: 18836483; PMCID: PMC2768269.
[39]. Pinter M, Trauner M, Peck-Radosavljevic M, Sieghart W. Cancer, and liver cirrhosis: implications on prognosis and management. ESMO Open. 2016 Mar 17;1(2):e000042. DOI: 10.1136/esmoopen-2016-000042. PMID: 27843598; PMCID: PMC5070280.
[40]. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957 Jul;28(1):56-63. DOI: 10.1093/ajcp/28.1.56. PMID: 13458125.
[41]. Rottiers V, Näär AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):239-50. DOI: 10.1038/nrm3313. Erratum in: Nat Rev Mol Cell Biol. 2012 May;13(5). DOI:10.1038/nrm3328. PMID: 22436747; PMCID: PMC4021399.
[42]. Ruan ZP, Xu R, Lv Y, Tian T, Wang WJ, Guo H, Nan KJ. PTEN enhances the sensitivity of human hepatocellular carcinoma cells to sorafenib. Oncol Res. 2012;20(2-3):113-21. DOI: 10.3727/096504012x13477145152995. PMID: 23193917.
[43]. Saad Y, El-Serafy M, Eldin MS, Abdellatif Z, Khatab H, Elbaz T, Elgarem H. New genetic markers for diagnosis of hepatitis C related hepatocellular carcinoma in Egyptian patients. J Gastrointestin Liver Dis. 2013 Dec;22(4):419-25. PMID: 24369324.
[44]. Shyu YC, Lee TL, Lu MJ, Chen JR, Chien RN, Chen HY, Lin JF, Tsou AP, Chen YH, Hsieh CW, Huang TS. miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma. J Transl Med. 2016 Jul 2;14(1):200. DOI: 10.1186/s12967-016-0956-z. PMID: 27370270; PMCID: PMC4930569.
[45]. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. DOI: 10.3322/caac.21387. Epub 2017 Jan 5. PMID: 28055103.
[46]. Sun J, Lu H, Wang X, Jin H. MicroRNAs in hepatocellular carcinoma: regulation, function, and clinical implications. ScientificWorldJournal. 2013;2013:924206. DOI: 10.1155/2013/924206. Epub 2013 Feb 4. PMID: 23431261; PMCID: PMC3575633.
[47]. Tan W, Li Y, Lim SG, Tan TM. miR-106b-25/miR-17-92 clusters: polycistrons with oncogenic roles in hepatocellular carcinoma. World J Gastroenterol. 2014 May 28;20(20):5962-72. DOI: 10.3748/wjg.v20.i20.5962. PMID: 24876719; PMCID: PMC4033436.
[48]. Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, Kuroda M. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS One. 2009;4(5):e5532. DOI: 10.1371/journal.pone.0005532. Epub 2009 May 14. PMID: 19440243; PMCID: PMC2678255.
[49]. Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev. 2016 Jan;25(1):16-27. DOI: 10.1158/1055-9965.EPI-15-0578. Epub 2015 Dec 14. PMID: 26667886.
[50]. Tsitsiou E, Lindsay MA. microRNAs and the immune response. CurrOpinPharmacol. 2009 Aug;9(4):514-20. DOI: 10.1016/j.coph.2009.05.003. Epub 2009 Jun 12. PMID: 19525145; PMCID: PMC2742742.
[51]. Tsou AP, Chuang YC, Su JY, Yang CW, Liao YL, Liu WK, Chiu JH, Chou CK. Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers. J Biomed Sci. 2003;10(6 Pt 1):625-35. DOI: 10.1159/000073528. PMID: 14576465.
[52]. Uhlén M, Björling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C, Berglund L, Bergström K, Brumer H, Cerjan D, Ekström M, Elobeid A, Eriksson C, Fagerberg L, Falk R, Fall J, Forsberg M, Björklund MG, Gumbel K, Halimi A, Hallin I, Hamsten C, Hansson M, Hedhammar M, Hercules G, Kampf C, Larsson K, Lindskog M, Lodewyckx W, Lund J, Lundeberg J, Magnusson K, Malm E, Nilsson P, Odling J, Oksvold P, Olsson I, Oster E, Ottosson J, Paavilainen L, Persson A, Rimini R, Rockberg J, Runeson M, Sivertsson A, Sköllermo A, Steen J, Stenvall M, Sterky F, Strömberg S, Sundberg M, Tegel H, Tourle S, Wahlund E, Waldén A, Wan J, Wernérus H, Westberg J, Wester K, Wrethagen U, Xu LL, Hober S, Pontén F. A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics. 2005 Dec;4(12):1920-32. DOI: 10.1074/mcp.M500279-MCP200. Epub 2005 Aug 27. PMID: 16127175.
[53]. Uotila M, Ruoslahti E, Engvall E. Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alpha-fetoprotein. J Immunol Methods. 1981;42(1):11-5. DOI: 10.1016/0022-1759(81)90219-2. PMID: 6165775.
[54]. Van Haaften G, Agami R. Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev. 2010 Jan 1;24(1):1-4. DOI: 10.1101/gad.1887110. PMID: 20047995; PMCID: PMC2802185.
[55]. Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P, Dienes HP, Odenthal M. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology. 2008 Apr;47(4):1223-32. DOI: 10.1002/hep.22158. PMID: 18307259.
[56]. Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, Li G, Wang L. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012 Apr 1;130(7):1639-48. DOI: 10.1002/ijc.26165. Epub 2011 Jul 28. PMID: 21544812.
[57]. Wang C, Xiao Y, Hu Z, Chen Y, Liu N, Hu G. PEG10 directly regulated by E2Fs might have a role in the development of hepatocellular carcinoma. FEBS Lett. 2008 Aug 6;582(18):2793-8. DOI: 10.1016/j.febslet.2008.07.009. Epub 2008 Jul 14. PMID: 18625225.
[58]. Wang SH, Yeh SH, Lin WH, Wang HY, Chen DS, Chen PJ. Identification of androgen response elements in the enhancer I of hepatitis B virus: a mechanism for sex disparity in chronic hepatitis B. Hepatology. 2009 Nov;50(5):1392-402. DOI: 10.1002/hep.23163. PMID: 19670412.
[59]. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009 Mar;11(3):228-34. DOI: 10.1038/ncb0309-228. PMID: 19255566.
[60]. Xie H, Sun L, Lodish HF. Targeting microRNAs in obesity. Expert OpinTher Targets. 2009 Oct;13(10):1227-38. DOI: 10.1517/14728220903190707. PMID: 19650761; PMCID: PMC3197810.
[61]. Yang W, Lu Y, Xu Y, Xu L, Zheng W, Wu Y, Li L, Shen P. Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs). J Biol Chem. 2012 Nov 23;287(48):40140-9. DOI: 10.1074/jbc.M112.348763. Epub 2012 Aug 20. PMID: 22908233; PMCID: PMC3504728.
[62]. Zhu H, Han C, Wu T. MiR-17-92 cluster promotes hepatocarcinogenesis. Carcinogenesis. 2015 Oct;36(10):1213-22. DOI: 10.1093/carcin/bgv112. Epub 2015 Aug 1. PMID: 26233958; PMCID: PMC4794620.
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