Silymarin-mediated regulation of the cell cycle and DNA damage response exerts antitumor activity in human hepatocellular carcinoma

• Published in: Oncology letters Vol. 15; no. 1; pp. 885 - 892
• Main Authors: Cui, Hong, Li, Tie-Ling, Guo, Hai-Feng, Wang, Jia-Liang, Xue, Ping, Zhang, Ying, Fan, Jing-Hui, Li, Zhi-Ping, Gao, Yue-Juan
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.01.2018; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Annealing; Care and treatment; Cell cycle; Cell division; Deoxyribonucleic acid; Development and progression; DNA; DNA damage; Gene expression; Genetic aspects; Health aspects; Hepatocellular carcinoma; Liver cancer; Oncology; Plant products; Proteins; Studies; DNA topoisomerase 2-binding protein 1; differential co-expression network; silymarin; hepatocellular carcinoma; differential modules
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2017.7425

A novel module-search algorithm method was used to screen for potential signatures and investigate the molecular mechanisms of inhibiting hepatocellular carcinoma (HCC) growth following treatment with silymarin (SM). The modules algorithm was used to identify the modules via three major steps: i) Seed gene selection; ii) module search by seed expansion and entropy minimization; and iii) module refinement. The statistical significance of modules was computed to select the differential modules (DMs), followed by the identification of core modules using the attract method. Pathway analysis for core modules was implemented to identify the biological functions associated with the disease. Subsequently, results were verified in an independent sample set using reverse transcription polymerase chain reaction (RT-PCR). In total, 18 seed genes and 12 DMs (modules 1-12) were identified. The core modules were isolated using gene expression data. Overall, there were 4 core modules (modules 11, 5, 6 and 12). Additionally, DNA topoisomerase 2-binding protein 1 ( ), non-structural maintenance of chromosomes condensing I complex subunit H, nucleolar and spindle associated protein 1 ( ) and cell division cycle associated 3 ( ) were the initial seed genes of module 11, 5, 6 and 12, respectively. Pathway results revealed that cell cycle signaling pathway was enriched by all core modules simultaneously. RT-PCR results indicated that the level of and in SM-treated HCC samples was markedly decreased compared with that in non-SM-treated HCC. No statistically significant difference between the transcriptional levels of in SM-treated and non-treated HCC groups was identified, although expression was increased in the treated group compared with the untreated group. Furthermore, although the expression level of and in the SM-treated group was decreased compared with that in the normal group, no significant difference was observed. From the results of the present study it can be inferred that , and of the core modules may serve notable functions in SM-associated growth suppression of HCC.