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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Molecule mechanisms of Ganoderma lucidum treated hepatocellular carcinoma based on the transcriptional profiles and
Chenchen Tang1, Ruolin Zhao2, Hongmei Ni3
1Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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.
Insights
Ganoderma lucidum extract (GLE) inhibits tumor growth in mice. Researchers identified key microRNAs and mRNAs involved in this process, suggesting potential biomarkers for evaluating GLE efficacy in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Ganoderma lucidum (GLE) shows promise in treating cancers like pancreatic cancer and hepatocellular carcinoma.
- The precise molecular mechanisms of GLE's therapeutic effects remain largely unknown.
- Understanding these mechanisms is crucial for optimizing cancer treatment strategies.
Purpose of the Study:
- To investigate the therapeutic efficacy of Ganoderma lucidum extract (GLE) in a mouse model of hepatocellular carcinoma (Hepa1-6).
- To identify differentially expressed microRNAs (DE-miRNAs) and messenger RNAs (DE-mRNAs) affected by GLE treatment.
- To elucidate the molecular pathways and potential biomarkers involved in GLE-mediated tumor inhibition.
Main Methods:
- Hepa1-6 bearing C57 BL/6 mouse model was used to assess GLE's anti-tumor effects.
- MicroRNA (miRNA) and messenger RNA (mRNA) profiling was performed on tumor tissues.
- Bioinformatic analyses including network construction (miRNA-target, protein-protein interaction) and qRT-PCR were employed.
Main Results:
- GLE significantly inhibited tumor growth in the Hepa1-6 mouse model.
- 25 differentially expressed miRNAs (24 up, 1 down) and 76 differentially expressed mRNAs were identified.
- Eight hub miRNAs were identified, and five key mRNAs (Cntn1, Irs1, Nfkbia, Rybp, Ywhaz) were found to be downregulated by GLE.
- Four specific miRNAs were identified as potential regulators of these downregulated mRNAs.
Conclusions:
- Ganoderma lucidum extract demonstrates significant anti-tumor activity in hepatocellular carcinoma.
- Specific miRNAs (mmu-mir-23a-5p, -3102-3p, -337-3p, -467a-3p) may play a role in mediating GLE's effects by downregulating key genes.
- These miRNAs represent potential biomarkers for assessing the efficacy of Ganoderma lucidum in cancer therapy.
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