Effect of Flavonoid Quercetin in MicroRNA and Transcription Factor Regulatory Network in Hepatocellular Carcinoma

Flavonoid Quercetin in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma is the second most common cause of death due to cancer. Flavonoids have the ability to control cell division and proliferation in cell biology. In medical science, flavonoids show important effects in cancer prevention and therapy. In this research paper, the effect of flavonoid quercetin on the microRNAs and transcription factors related with hepatocellular carcinoma has been investigated. From microarray dataset, regulatory relationship among miRNAs, TFs and target genes from various databases, are analyzed for hepatocellular carcinoma using CMTCN, a web tool. Regulatory interactions of transcription factors and miRNAs and their target genes play important role in cancer science. In presence of flavonoid quercetin, the up and down regulated genes with their regulators are analyzed in details. Gene network with 500 upregulated genes, shows 109 nodes and 132 edges. Result of gene enrichment analysis with KEGG pathway shows that among 24 genes, 7 genes are related with cancer. Among them P53, MDM2 and PTEN are related with p53 signaling pathway. Gene network with top 500 downregulated genes, illustrates network topology with 146 nodes and 177 edges. Gene enrichment analysis using KEGG pathways, reveals that among 36 genes 9 genes are related to cancer. These genes are APC, CTNNB1, PML, TP53, FOS, JUN, CEBPA, PTEN and Bcl 2. Target gene B-cell lymphoma 2 (Bcl 2), which is down regulated in presence of flavonoid quercetin, has been identified. Here quercetin binds to the BH3 domain of Bcl 2 protein and inhibits its activity which leads to cancer cell apoptosis. Several miRNAs can post-transcriptionally regulates the gene expression of Bcl2 gene. Gene network shows that miRNA has-mir-590 inhibits Bcl 2 target gene. NR112 transcription factor can regulate both target gene and its inhibitor miRNA. By analyzing transcription factor- target gene and miRNA- target gene binding the role of flavonoid quercetin in hepatocellular carcinoma can be elucidated.

Keywords: Gene regulatory network, miRNA, Transcription factor, flavonoid, quercetin, B-cell lymphoma 2 gene

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References

Ashrafizadeh, M., Ahmadi, Z., Farkhondeh, T., & Samarghandian, S. (2019). Autophagy as a molecular target of quercetin underlying its protective effects in human diseases. Archives of Physiology and Biochemistry, 1-9.
Avior, Y., Bomze, D., Ramon, O., & Nahmias, Y. (2013). Flavonoids as dietary regulators of nuclear receptor activity. Food & function, 4(6), 831-844.
Balogh, J., David Victor III, E. H. A., Burroughs, S. G., Boktour, M., Saharia, A., Li, X., ... & Monsour Jr, H. P. (2016). Hepatocellular carcinoma: a review. Journal of hepatocellular carcinoma, 3, 41.
Fernández-Palanca, P., Fondevila, F., Méndez-Blanco, C., Tuñón, M. J., González-Gallego, J., & Mauriz, J. L. (2019). Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review. Nutrients, 11(12), 2875.
http://www.ncbi.nlm.nih. gov/geo/geo2r/
http://www.ncbi.nlmNih.gov/geo
Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1-13.
Li, R., Chen, H., Jiang, S., Li, W., Li, H., Zhang, Z., ... & Bo, X. (2018). CMTCN: a web tool for investigating cancer-specific microRNA and transcription factor co-regulatory networks. PeerJ, 6, e5951.
López Lázaro, M., Burgos Morón, E., Tena, J. D., & Calderón Montaño, J. M. (2013). Consumption of the Dietary Flavonoids Quercetin, Luteolin and Kaempferol and Overall Risk of Cancer-A Review and Meta-Analysis of the Epidemiological Data. WebmedCentral, 4 (5).
Mohamed, R. H., Abu-Shahba, N., Mahmoud, M., Abdelfattah, A. M., Zakaria, W., & ElHefnawi, M. (2019). Co-regulatory Network of oncosuppressor miRNAs and transcription Factors for pathology of Human Hepatic Cancer stem Cells (HCsC). Scientific reports, 9(1), 5564.
Niu, Z. S., Niu, X. J., & Wang, W. H. (2016). Genetic alterations in hepatocellular carcinoma: An update. World journal of gastroenterology, 22(41), 9069.
Notas, G., Nifli, A. P., Kampa, M., Pelekanou, V., Alexaki, V. I., Theodoropoulos, P., ... & Castanas, E. (2012). Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells. The Journal of nutritional biochemistry, 23(6), 656-666.
Peng, C., Wang, M., Shen, Y., Feng, H., & Li, A. (2013). Reconstruction and analysis of transcription factor–miRNA co-regulatory feed-forward loops in human cancers using filter-wrapper feature selection. PloS one, 8(10), e78197.
Peng, Y., & Croce, C. M. (2016). The role of MicroRNAs in human cancer. Signal transduction and targeted therapy, 1, 15004.
Primikyri, A., Chatziathanasiadou, M. V., Karali, E., Kostaras, E., Mantzaris, M. D., Hatzimichael, E., ... & Gerothanassis, I. P. (2014). Direct binding of Bcl-2 family proteins by quercetin triggers its pro-apoptotic activity. ACS chemical biology, 9(12), 2737-2741.
Tsujimoto, Y. (1998). Role of Bcl‐2 family proteins in apoptosis: apoptosomes or mitochondria?. Genes to cells, 3(11), 697-707.
van Dijk, M., & Bonvin, A. M. (2009). 3D-DART: a DNA structure modelling server. Nucleic acids research, 37(suppl_2), W235-W239.
Veeramuthu, D., Raja, W. R. T., Al-Dhabi, N. A., & Savarimuthu, I. (2017). Flavonoids: Anticancer Properties. Flavonoids: From Biosynthesis to Human Health, 287.
Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F.T., de Beer, T.A.P., Rempfer, C., Bordoli, L., Lepore, R., Schwede, T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296-W303 (2018)
Zaheer, U., Faheem, M., Qadri, I., Begum, N., Yassine, H. M., Al Thani, A. A., & Mathew, S. (2019). Expression profile of MicroRNA: An Emerging Hallmark of Cancer. Current pharmaceutical design, 25(6), 642-653.
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How to Cite
Basu, A. “Effect of Flavonoid Quercetin in MicroRNA and Transcription Factor Regulatory Network in Hepatocellular Carcinoma”. International Journal of Advancement in Life Sciences Research, Vol. 3, no. 1, Jan. 2020, pp. 16-23, http://ijalsr.org/index.php/journal/article/view/78.
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Research Articles