MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC)
| Autor: | Hiroshi Nishioka, Émilie A. Graham, Majed Jambi, Jean-François Mallet, Kohei Homma, Chantal Matar |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis Primary Cell Culture Breast Neoplasms Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Movement Polysaccharides Cancer stem cell Cell Line Tumor microRNA Active hexose correlated compound medicine Animals Humans Immunologic Factors skin and connective tissue diseases Mycelium Cell Proliferation Progenitor Pharmacology Mice Inbred BALB C Mushroom biology Gene Expression Profiling fungi Tenascin C Tenascin medicine.disease Xenograft Model Antitumor Assays Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology Biochemistry 030220 oncology & carcinogenesis Immunology Neoplastic Stem Cells biology.protein Molecular Medicine Female Research Paper |
| Zdroj: | Cancer Biology & Therapy. 18:765-774 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2017.1373211 |
| Popis: | Purpose: Many breast cancer patients use natural compounds in their battle against breast cancer. Active Hexose Correlated Compound (AHCC®) is a cultured mushroom mycelium extract shown to favorably modulate the immune system and alleviate cancer burden. Cancer Stem cells (CSCs) are a subset of highly tumorigenic cancer cells that are thought to be responsible for recurrence. CSCs can be epigenetically regulated by microRNAs (miRNAs). We hypothesized that AHCC may influence CSCs by modulating tumor-suppressor or oncogenic miRNAs. Methods: Functionally-enriched stem and progenitor pools (FESPP) were isolated in the form of mammospheres from MDA-MB-231, MCF-7, and 4T1 cells, exposed to AHCC in both regular and primary culture from Balb/c mice, and analyzed by visual counting and flow cytometry. Cell motility was also observed in MDA-MB-231 cells. Profiling and RT-qPCR were performed to determine AHCC influence on miRNAs in MDA-MB-231 mammospheres. Additionally, Balb/c mice were orally gavaged with AHCC, and tumor growth parameters and miR-335 expression were analyzed. MDA-MB-231 cells were transfected with miR-335 and analyzed by western blot. Results: We demonstrated that AHCC reduced mammosphere growth in three cell lines and in primary culture, prevented cell migration, and upregulated miR-335 expression in MDA-MB-231 cells and mouse tumor samples. Among the differentially regulated miRNAs in CSCs, we focused on tumor suppressor miR-335, known to target extracellular matrix protein Tenascin C (TNC). TNC is involved in CSC immune evasion pathways. In MDA-MB-231, inhibition of miR-335 increased TNC protein expression. Conclusions: These results support that AHCC limits FESPP growth, partly by targeting miRNA pathways. |
| Databáze: | OpenAIRE |
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