Molecule mechanisms of Ganoderma lucidum treated hepatocellular carcinoma based on the transcriptional profiles and miRNA-target network.

ABSTRACT

Ganoderma lucidum has salutary effects on tumor treatment, including pancreatic cancer and hepatocellular carcinoma. However, the molecular mechanisms underlying Ganoderma lucidum therapy is obscure. In this study, the Hepa1-6-bearing C57 BL/6 mouse model was utilized to explore the therapeutic efficacy of Ganoderma lucidum extract (GLE), documenting that it could effectively inhibit tumor growth. The microRNA (miRNA) profiles of GLE-treated and untreated mice were detected, and 25 differentially expressed (DE) miRNAs were determined, including 24 up-expressed and one down-expressed miRNAs. Using the ClusterOne algorithm, 8 hub miRNAs were isolated from the established miRNA-target network. The qRT-PCR assay demonstrated that these 8 miRNAs were up-expressed in the GLE treated tumor mice. Furthermore, the mRNA profiles showed that there are 76 DE mRNAs between GLE treated and model groups. The protein-protein interaction (PPI) network shows that Cntn1, Irs1, Nfkbia, Rybp and Ywhaz playing important roles, and qRT-PCR further revealed they were down-expressed in GLE treated Hepa1-6-bearing C57 BL/6 mice. The rebuilt miRNA-target network was shown that these 5 mRNAs were regulated by mmu-mir-23a-5p, -3102-3p, -337-3p, and -467a-3p, respectively. This study suggested that these 4 interesting miRNAs were potential biomarkers for evaluation of GLE efficacy, which may down-regulate the expression of Cntn1, Irs1, Nfkbia, Rybp and Ywhaz, and mediate many signaling pathways occurring in tumor treatment.