Validation of MicroRNAs (miRNAs) in the Early Diagnosis and Treatment of Hepatocellular Carcinoma (HCC)
Abstract
Abstract Views: 113Late diagnosis and delayed presentation of HCV is among the leading causes of liver cancer. MicroRNAs (miRNAs) are non-coding molecules involved in the regulation of a variety of functions happening in the cell, in both healthy and diseased states. Dysregulation of miRNAs is observed in different diseases, especially in liver cancer including hepatocellular carcinoma (HCC). The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for the diagnosis of HCC at an early stage in order to minimize the chances of liver cancer. Circulating miRNAs are novel and minimally invasive markers used for the early detection of HCV based HCC. In this review, the current progress on the potential role of miRNAs as biomarkers used for the detection of HCC and other therapeutic targets was summarized. We concluded that the expression of miRNAs is upregulated in the patients of HCC as compared with healthy individuals. An in-depth study of miRNAs as genetic biomarkers in the patients of HCC will improve its diagnosis. It will also improve the prognosis of early stage HCC patients. Furthermore, it will also help to identify a suitable and effective therapeutic target so as to reduce the chances of the failure of chemotherapy.
Keywords: biogenesis, biomarkers, hepatocellular carcinoma (HCC), microRNAs (miRNAs), mRNA
Copyright (c) Iqra Khalid, Azra Quraishi, Freeha Fiaz
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Schiefelbein E, Zekri AR, Newton DW, et al. Hepatitis C virus and other risk factors in hepatocellular carcinoma. Acta Virol. 2012;56(3):235-240. doi:10.4149/av_2012_03_235
Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. Journal of hepatology. 2020 Feb 1;72(2):250-61.
Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. HPB (Oxford). 2005;7(1):26-34. doi:10.1080/13651820410024049
Chou, R., C. Cuevas, R. Fu, B. Devine, N. Wasson, A. Ginsburg, B. Zakher, M. Pappas, E. Graham and S.D. Sulivan. 2015. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis Annals of Internal Medicine, 162:697-711.
Toyoda, H., T. Kumada, T. Tada, Y. Kaneoka, A. Maeda, M. Korenaga, M. Mizokami and H. Narimatsu. 2016. Serum WFA+‐M2BP levels as a prognostic factor in patients with early hepatocellular carcinoma undergoing curative resection. Liver International, 36:293-301.
Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nature reviews Drug discovery. 2013 Nov;12(11):847-65.
Hwang, H. W., E. A. Wentzel and J. T. Mendell. 2007. A hexanucleotide element directs microRNA nuclear import. Science, 315:97-100
Ling H, Zhang W, Calin GA. Principles of microRNA involvement in human cancers. Chinese journal of cancer. 2011 Nov;30(11):739.
Giza DE, Vasilescu C, Calin GA. Key principles of miRNA involvement in human diseases. Discoveries. 2014 Oct;2(4).
Lee, R. C., R. L. Feinbaum and V. Ambros. 1993. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 Cell. 75:843-854.
MacFarlane LA, R Murphy P. MicroRNA: biogenesis, function and role in cancer. Current genomics. 2010 Nov 1;11(7):537-61.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. cell. 2004 Jan 23;116(2):281-97
Reddy, K.B. MicroRNA (miRNA) in cancer. Cancer Cell Int 15, 38 (2015). https://doi.org/10.1186/s12935-015-0185-1
Deng, S., G. A. Calin, C. M. Croce, G. Coukos and L. Zhang. 2008. Mechanisms of microRNA deregulation in human cancer Cell cycle, 7:2643-2646.
Debes JD, Romagnoli PA, Prieto J, Arrese M, Mattos AZ, Boonstra A, Escalon Consortium. Serum Biomarkers for the Prediction of Hepatocellular Carcinoma. Cancers. 2021 Jan;13(7):1681.
Chim SS, Shing TK, Hung EC, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54(3):482-490. doi:10.1373/clinchem.2007.097972
Kota J, Chivukula RR, O'Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137(6):1005-1017. doi:10.1016/j.cell.2009.04.021
Eiring AM, Harb JG, Neviani P, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140(5):652-665. doi:10.1016/j.cell.2010.01.007
Almeida MQ, Stratakis CA. How does cAMP/protein kinase A signaling lead to tumors in the adrenal cortex and other tissues?. Mol Cell Endocrinol. 2011;336(1-2):162-168. doi:10.1016/j.mce.2010.11.018
Hutvágner, G., J. McLachlan, A. E. Pasquinelli, É. Bálint, T. Tuschl and P. D. Zamore. 2001. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA Science, 293:834-838.
Toffanin, S., Y. Hoshida, A. Lachenmayer, A. Villanueva, L. Cabellos, B. Minguez, R. Savic, S. C. Ward, S. Thung, D. Y. Chiang and C. Alsinet. 2011. MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a. Gastroenterology, 140:1618-1628.
Sadri Nahand, J., Bokharaei‐Salim, F., Salmaninejad, A., Nesaei, A., Mohajeri, F., Moshtzan, A., Tabibzadeh, A., Karimzadeh, M., Moghoofei, M., Marjani, A. and S. Yaghoubi. 2019. microRNAs: Key players in virus‐associated hepatocellular carcinoma. Journal of cellular physiology, 234(8), pp.12188-12225.
Hsu YC, Wu CY, Lin JT. Hepatitis C virus infection, antiviral therapy, and risk of hepatocellular carcinoma. Semin Oncol. 2015;42(2):329-338. doi:10.1053/j.seminoncol.2014.12.023
Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma?. Hepatology. 2013 Feb;57(2):840-7.
Chitapanarux T, Phornphutkul K. Risk Factors for the Development of Hepatocellular Carcinoma in Thailand. J Clin Transl Hepatol. 2015;3(3):182-188. doi:10.14218/JCTH.2015.00025
Wang B, Xi Y. Challenges for MicroRNA Microarray Data Analysis. Microarrays (Basel). 2013;2(2):34-50. doi:10.3390/microarrays2020034
Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol. 2009;4:199-227. doi:10.1146/annurev.pathol.4.110807.092222
Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6(9):674-687. doi:10.1038/nrc1934
Zucman-Rossi, J., A. Villanueva, J. C. Nault and J. M. Llovet. 2015. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology, 149:1226-1239.
Aravalli, R. N., C. J. Steer and E. N. Cressman. 2008. Molecular mechanisms of hepatocellular carcinoma. Hepatology, 48(6), pp.2047-2063.
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557-2576. doi:10.1053/j.gastro.2007.04.061
Wang W, Wei C. Advances in the early diagnosis of hepatocellular carcinoma. Genes & Diseases. 2020 Sep 1;7(3):308-19.
Tavazoie, S.F., C. Alarcón, T. Oskarsson, D. Padua, Q. Wang, P .D. Bos,W. L. Gerald and J. Massagué. 2008. Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451(7175), 147.
Yang, Y. F., F. Wang, J. J. Xiao, Y. Song, Y. Y. Zhao, Y. Cao, Y. H. Bei and C. Q. Yang. 2014. MiR-222 overexpression promotes proliferation of human hepatocellular carcinoma HepG2 cells by downregulating p27. International journal of clinical and experimental medicine, 7:893.
He, L., Hannon, G. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5, 522–531 (2004). https://doi.org/10.1038/nrg1379
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857-866. doi:10.1038/nrc1997
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-269. doi:10.1038/nrc1840
Huang, X. H., Q. Wang, J. S. Chen, X. H. Fu, X. L. Chen, L. Z. Chen, W. Li, J. Bi, L. J. Zhang, Q. Fu and W. T. Zeng. 2009. Bead‐based microarray analysis of microRNA expression in hepatocellular carcinoma: miR‐338 is downregulated. Hepatology research, 39:786-794.
Wang Y, Toh HC, Chow P, et al. MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms. FASEB J. 2012;26(7):3032-3041. doi:10.1096/fj.11-201855
Hurst DR, Edmonds MD, Welch DR. Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res. 2009;69(19):7495-7498. doi:10.1158/0008-5472.CAN-09-2111
Rosenfeld N, Aharonov R, Meiri E, et al. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008;26(4):462-469. doi:10.1038/nbt1392
Lu, J., G. Getz, E. A. Miska, E. Alvarez-Saavedra, J. Lamb, D. Peck, A. Sweet-Cordero, B. L. Ebert, R. H. Mak, A. A. Ferrando and J. R. Downing. 2005. MicroRNA expression profiles classify human cancers. nature, 435:834
Lawrie, C. H., S. Gal, H. M. Dunlop, B. Pushkaran, A. P. Liggins, K. Pulford, A. H. Banham, F. Pezzella, J. Boultwood, J. S. Wainscoat and C. S. Hatton. 2008. Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma. British journal of haematology, 141:672-675.
Tsujiura, M., D. Ichikawa, S. Komatsu, A. Shiozaki, H. Takeshita, T. Kosuga, H. Konishi, R. Morimura, K. Deguchi, H. Fujiwara and K. Okamoto. 2010. Circulating microRNAs in plasma of patients with gastric cancers. British journal of cancer, 102:1174.
Ho AS, Huang X, Cao H, et al. Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. Transl Oncol. 2010;3(2):109-113. doi:10.1593/tlo.09256
Wong, T. S., X. B. Liu, B. Y. H. Wong, R. W. M. Ng, A. P. W. Yuen and W. I. Wei. 2008. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clinical Cancer Research, 14:2588-2592.
Yamamoto, Y., N. Kosaka, M. Tanaka, F. Koizumi, Y. Kanai, T. Mizutani, Y. Murakami, M. Kuroda, A. Miyajima, T. Kato and T. Ochiya. 2009. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers, 14:529-538.
Hayes, C. N. and K. Chayama. 2016. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. International journal of molecular sciences, 17:280.
Gramantieri, L., M. Ferracin, F. Fornari, A. Veronese, S. Sabbioni, C. G. Liu, G. A. Calin, C. Giovannini, E. Ferrazzi, G. L. Grazi and C. M. Croce. 2007. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer research, 67:6092-6099.
Connolly, E., M. Melegari, P. Landgraf, T. Tchaikovskaya, B. C. Tennant, B. L. Slagle, L. E. Rogler, M. Zavolan, T. Tuschl and C. E. Rogler. 2008. Elevated expression of the miR-17–92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. The American journal of pathology, 173:856-864.
Su, H., J. R. Yang, T. Xu, J. Huang, L. Xu, Y. Yuan and S. M. Zhuang. 2009. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer research, 69:1135-1142.
Jiang, J., Y. Gusev, I. Aderca, T. A. Mettler, D. M. Nagorney, D. J. Brackett, L. R. Roberts and T. D. Schmittgen. 2008. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clinical cancer research, 14:419-427.
Varnholt, H., U. Drebber, F. Schulze, I. Wedemeyer, P. Schirmacher, H. P. Dienes and M. Odenthal. 2008. MicroRNA gene expression profile of hepatitis C virus–associated hepatocellular carcinoma. Hepatology, 47:1223-1232.
Huang, X. H., Q. Wang, J. S. Chen, X. H. Fu, X. L. Chen, L. Z. Chen, W. Li, J. Bi, L. J. Zhang, Q. Fu and W. T. Zeng. 2009. Bead‐based microarray analysis of microRNA expression in hepatocellular carcinoma: miR‐338 is downregulated. Hepatology research, 39:786-794.
Zou, C. D., W. M. Zhao, X. N. Wang, Q. Li, H. Huang, W. P. Cheng, J. F. Jin, H. Zhang, M. J. Wu, S. Tai and C. X. Zou. 2016. MicroRNA-107: a novel promoter of tumor progression that targets the CPEB3/EGFR axis in human hepatocellular carcinoma. Oncotarget, 7:266.
Wong, Q. W., A. K. Ching, A. W. Chan, K. W. Choy, K. F. To, P. B. Lai and N. Wong. 2010. MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clinical Cancer Research, 16:867-875.
Wang, Y., A. T. Lee, J. Z. Ma, J. Wang, J. Ren, Y. Yang, E. Tantoso, K. B. Li, L. L. J. Ooi, P. Tan and C. G. Lee. 2008. Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. Journal of Biological Chemistry, 283:13205-13215.
Copyright (c) 2021 Iqra Khalid, Azra Quraishi, Freeha Fiaz
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