PMID- 28886271 OWN - NLM STAT- MEDLINE DCOM- 20180705 LR - 20240327 IS - 1555-8576 (Electronic) IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 18 IP - 10 DP - 2017 Oct 3 TI - MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC). PG - 765-774 LID - 10.1080/15384047.2017.1373211 [doi] AB - PURPOSE: Many breast cancer patients use natural compounds in their battle against breast cancer. Active Hexose Correlated Compound (AHCC(R)) 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. FAU - Graham, Emilie A AU - Graham EA AD - a Interdisciplinary Health Sciences , University of Ottawa , Ottawa , Canada. FAU - Mallet, Jean-Francois AU - Mallet JF AD - b Cellular and Molecular Medicine, Faculty of Medicine , University of Ottawa , Ottawa, Ontario , Canada. FAU - Jambi, Majed AU - Jambi M AD - b Cellular and Molecular Medicine, Faculty of Medicine , University of Ottawa , Ottawa, Ontario , Canada. FAU - Nishioka, Hiroshi AU - Nishioka H AD - c R&D Division Amino Up Chemical Co, Ltd , Sapporo , Japan. FAU - Homma, Kohei AU - Homma K AD - c R&D Division Amino Up Chemical Co, Ltd , Sapporo , Japan. FAU - Matar, Chantal AU - Matar C AD - a Interdisciplinary Health Sciences , University of Ottawa , Ottawa , Canada. AD - b Cellular and Molecular Medicine, Faculty of Medicine , University of Ottawa , Ottawa, Ontario , Canada. LA - eng PT - Journal Article DEP - 20170908 PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (Immunologic Factors) RN - 0 (MIRN335 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Mirn335 microRNA, mouse) RN - 0 (Polysaccharides) RN - 0 (Tenascin) RN - S1W5KTD68Y (Active Hexose Correlated Compound) SB - IM MH - Animals MH - Breast Neoplasms/genetics/immunology/*prevention & control MH - Carcinogenesis/drug effects/genetics/immunology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Epigenesis, Genetic/drug effects MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Immunologic Factors/*pharmacology/therapeutic use MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/immunology/metabolism MH - Neoplastic Stem Cells/*drug effects/immunology/metabolism MH - Polysaccharides/*pharmacology/therapeutic use MH - Primary Cell Culture MH - Tenascin/genetics/immunology/metabolism MH - Up-Regulation MH - Xenograft Model Antitumor Assays PMC - PMC5678688 OTO - NOTNLM OT - AHCC OT - Tenascin C OT - breast cancer OT - cancer stem cell OT - microRNA EDAT- 2017/09/09 06:00 MHDA- 2018/07/06 06:00 PMCR- 2018/09/08 CRDT- 2017/09/09 06:00 PHST- 2017/09/09 06:00 [pubmed] PHST- 2018/07/06 06:00 [medline] PHST- 2017/09/09 06:00 [entrez] PHST- 2018/09/08 00:00 [pmc-release] AID - 1373211 [pii] AID - 10.1080/15384047.2017.1373211 [doi] PST - ppublish SO - Cancer Biol Ther. 2017 Oct 3;18(10):765-774. doi: 10.1080/15384047.2017.1373211. Epub 2017 Sep 8.