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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.625 Facteur d'impact sur 5 ans: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019029549
pages 195-203

Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression

Zhenjiang Zhao
Department of Radiology, Luoyang Orthopedic Hospital of Henan Province, Zhengzhou City, Henan Province, 450000, China
Anshoo Malhotra
Post Graduate Institute of Medial Education and Research, India
Wu Yuan Seng
Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, MAHSA University, Selangor 42610, Malaysia


UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.


  1. Bellier J, De Wolf J, Hebbar M, Amrani ME, Desauw C, Leteurtre E, Pruvot FR, Porte H, Truant S. Repeated resections of hepatic and pulmonary metastases from colorectal cancer provide long-term survival. World J Surg. 2018;42:1171-9. .

  2. Kudo M, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J, Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018;3:37-46. .

  3. Biederman DM, Posham R, Durrani RJ, Titano JJ, Patel RS, Tabori NE, Nowakowski FS, Fischman AM, Lookstein RA, Kim E. Outcomes of radioembolization for unresectable hepatocellular carcinoma in patients with marginal functional hepatic reserve. Clin Imaging. 2018;47:34-4. .

  4. Marabelle A, Gray J. Tumor-targeted and immune-targeted monoclonal antibodies: going from passive to active immunotherapy. Ped Blood Cancer 2015;62:1317-25. .

  5. Munro MJ, Wickremesekera SK, Peng L, Tan ST, Itinte- ang T. Cancer stem cells in colorectal cancer: a review. J Clin Pathol. 2018;71:110-6. .

  6. Kristensen LS, Hansen TB, Ven0 MT, Kjems J. Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2018;37(5):555-65. .

  7. Smith SG, Koppolu BP, Ravindranathan S, Kurtz SL, Yang L, Katz MD, Zaharoff DA. Intravesical chitosan/ interleukin-12 immunotherapy induces tumor-specific systemic immunity against murine bladder cancer. Cancer Immunol Immunother. 2015;CII 64:689-96. .

  8. Pongor L, Kormos M, Hatzis C, Pusztai L, Szabo A, Gyorffy B. A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients. Gen Med. 2015;7:104. .

  9. Tsikrika FD, Avgeris M, Levis PK, Tokas T, Stravodimos K, Scorilas A. miR-221/222 cluster expression improves clinical stratification of non-muscle invasive bladder cancer(TaTl) patients' risk for short-term relapse and progression. Genes Chromo Cancer. 2018;57:150-61. .

  10. Ruike Y, Imanaka Y, Sato F, Shimizu K, Tsujimoto G. Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genom. 2010;11:137. .

  11. Mazard T, Boonsirikamchai P, Overman MJ, Asran MA, Choi H, Herron D, Eng C, Maru DM, Ychou M, Vauthey JN, Loyer EM, Kopetz S. Comparison of early radiological predictors of outcome in patients with colorectal cancer with unresectable hepatic metastases treated with bevacizumab. Gut. 2018;67:1095-102. .

  12. Higashide T, Inana G. Characterization of the gene for HRG4 [UNC119], a novel photoreceptor synaptic protein homologous to UNC-119. Genomics. 1999;57:446-50. .

  13. Lei B, Chai W, Wang Z, Liu R. Highly expressed UNC119 promotes hepatocellular carcinoma cell proliferation through Wnt/beta-catenin signaling and predicts a poor prognosis. Am J Can Res. 2015;5:3123-34. .

  14. Wei W, Liu B, Jiang H, Jin K, Xiang M. Requirement of the Mowat-Wilson syndrome gene Zeb2 in the differentiation and maintenance of non-photoreceptor cell types during retinal development. Mol Neurobiol. 2018;19:1-8. doi:10.1007/s12035-018-1186-6. .

  15. Chen KE, Richards AA, Ariffin JK, Ross IL, Sweet MJ, Kellie S, Kobe B, Martin JL. The mammalian DUF59 protein Fam96a forms two distinct types of domain-swapped dimer. Acta Crystallog D, Bio Crystallog. 2012;68:637-48. .

  16. Yang WR, Wang Y, Zhang JJ, Zhang JH, Lu C, Wang XZ. mTOR is involved in 17beta-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1. Mol Reprod Develop. 2015;82:305-14. .

  17. Singh M, Yelle N, Venugopal C, Singh SK. EMT: mechanisms and therapeutic implications. Pharmacol Ther. 2018;182:80-94. .

  18. McLarnon A. Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon cancer-a possible target for therapy. Nat Rev Gastroenterol Hepatol. 2012;9:4. .

  19. Menon KV, Hakeem AR, Heaton ND. Review article: liver transplantation for hepatocellular carcinoma-a critical appraisal of the current worldwide listing criteria. Alimentary Pharmacol Therap. 2014;40:893-902. .

  20. Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, Taylor-Robinson SD. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Exp Rev Gastroenterol Hepatol. 2009;3:353-67. .

  21. Simonetti RG, Camma C, Fiorello F, Politi F, D'Amico G, Pagliaro L. Hepatocellular carcinoma. A world-wide problem and the major risk factors. Digest Dis Sci. 1991;36:962-72. .

  22. Manne V, Handa P, Kowdley KV. Pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Clin Liver Dis. 2018;22:23-37. .

  23. Rodrigues SG, Maurer MH, Baumgartner I, De Gottardi A, Berzigotti A. Imaging and minimally invasive endo-vascular therapy in the management of portal vein thrombosis. Abdom Radiol (NY). 2018;43:1931-46 .

  24. Ackers I, Malgor R. Interrelationship of canonical and 29. non-canonical Wnt signalling pathways in chronic metabolic diseases. Diab Vasc Dis Res. 2018 ;15:3-13. .

  25. Mizukoshi E, Nakagawa H, Kitahara M, Yamashita T, Arai K, Sunagozaka H, Iida N, Fushimi K, Kaneko S. 30. Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma. Cancer Lett. 2015;369:242-9. .

  26. Ibrahim AA, Abdel Aleem MH, Abdella HM, Helmy A. Study of the role of insulin resistance as a risk factor in 31. HCV related hepatocellular carcinoma. J Egyptian Soc Parasitol. 2015;45:107-13. .

  27. Chen H, Liu D, Guo L, Cheng X, Guo N, Shi M. Chronic 32. psychological stress promotes lung metastatic colonization of circulating breast cancer cells by decorating a pre-metastatic niche through activating P-adrenergic signalin. J Pathol. 2018;244:49-60. .

  28. Qiu Y, Liu Y, Li WH, Zhang HQ, Tian XX, Fang WG. P2Y2 receptor promotes the migration and invasion of breast cancer cells via EMT-related genes Snail and E-cadherin. Oncol Rep. 2018;39:138-50. .

  29. Chen PC, Lee WY, Ling HH, Cheng CH, Chen KC, Lin CW. Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells. J Cell Physiol. 2018;233: 4972-80. .

  30. Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev. 2018;62:50-60. .

  31. Akcora BO, Storm G, Bansal R. Inhibition of canonical WNT signaling pathway by P-catenin/CBP inhibitor ICG-001 ameliorates liver fibrosis in vivo through suppression of stromal CXCL12. Biochim Biophys Acta Mol Basis Dis. 2018;1864:804-18. .

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