Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Autor:	Roghayeh Shahbazi, Chantal Matar, Jean-François Mallet, Nawal Alsadi
Rok vydání:	2021
Předmět:	breast cancer stem cells 0301 basic medicine Blueberry Plants Pharmaceutical Science Breast Neoplasms Biology medicine.disease_cause Article Analytical Chemistry Mice 03 medical and health sciences QD241-441 0302 clinical medicine Breast cancer N-RAS Downregulation and upregulation Cell Line Tumor Drug Discovery microRNA medicine Animals Humans Epigenetics Physical and Theoretical Chemistry epigenetics Forkhead Box Protein O1 FOXO1 Organic Chemistry Polyphenols medicine.disease Antineoplastic Agents Phytogenic microRNAs Gene Expression Regulation Neoplastic Blot 030104 developmental biology Chemistry (miscellaneous) Cell culture 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Molecular Medicine Female Stem cell Carcinogenesis
Zdroj:	Molecules Molecules, Vol 26, Iss 4330, p 4330 (2021) Volume 26 Issue 14
ISSN:	1420-3049
Popis:	Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb015037e6443fc7cdebb8bfbcff71f7 https://doi.org/10.3390/molecules26144330 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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