The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs

Abstract Background Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties o...

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Autores principales:	Demet Cansaran-Duman, Sevcan Yangın, Betül Çolak
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Vulpinic acid microRNA analysis Breast cancer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c87fb5c02321453da990fc01d86ca411
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spelling	oai:doaj.org-article:c87fb5c02321453da990fc01d86ca4112021-11-14T12:32:51ZThe role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs10.1186/s40659-021-00360-40717-6287https://doaj.org/article/c87fb5c02321453da990fc01d86ca4112021-11-01T00:00:00Zhttps://doi.org/10.1186/s40659-021-00360-4https://doaj.org/toc/0717-6287Abstract Background Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties of natural compounds are related to the regulation of microRNA (miRNA) expression. Therefore, changing the profile of miRNAs with the use of natural products is very important in cancer treatment. However, the role of vulpinic acid and related miRNAs in breast cancer progression remains unknown. Vulpinic acid, methyl (as2E)-2-(3-hydroxy-5-oxo-4-phenylfuran-2-ylidene)-2 phenylacetate, is a natural product extracted from the lichen species and shows an anticancer effect on different cancer cells. Methods This study examines the effects of vulpinic acid on the miRNA levels of breast cancer (MCF-7) cells and its relationship with cell proliferation and apoptosis levels. The antiproliferative effect of vulpinic acid was screened against MCF-7 breast cancer cells and MCF-12A breast epithelial cells using the xCELLigence real-time cell analysis system. We analyzed the altered miRNA expression profile in MCF-7 breast cancer cells versus MCF-12A cells following their response to vulpinic acid through microarray analysis. The microarray analysis results were confirmed through quantitative real-time PCR and bioinformatics analysis. Results The results of the miRNA array and bioinformatic analyses demonstrated that 12 miRNAs were specifically responsive to vulpinic acid in MCF-7 breast cancer cells. This is the first study to reveal that vulpinic acid inhibits the expression of 12 miRNAs and suppresses breast cancer cell proliferation. The study also revealed that vulpinic acid may downregulate the expression of 12 miRNAs by repressing the FOXO-3 gene. The miRNA targets were mainly found to play a role in the apoptosis, cell cycle and MAPK pathways. Moreover, Bcl-2, Bax, procaspase-3 and procaspase-9 protein levels were assessed by western blot analysis for validation of apoptosis at the protein level. Conclusion This study revealed the molecular mechanisms of vulpinic acid on breast cancer and showed that vulpinic acid regulates apoptosis signaling pathways by decreasing the expression of miRNAs. The miRNA expression patterns illuminate the underlying effect of vulpinic acid in breast cancer treatment. Graphical AbstractDemet Cansaran-DumanSevcan YangınBetül ÇolakBMCarticleVulpinic acidmicroRNA analysisBreast cancerBiology (General)QH301-705.5ENBiological Research, Vol 54, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vulpinic acid microRNA analysis Breast cancer Biology (General) QH301-705.5
spellingShingle	Vulpinic acid microRNA analysis Breast cancer Biology (General) QH301-705.5 Demet Cansaran-Duman Sevcan Yangın Betül Çolak The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
description	Abstract Background Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties of natural compounds are related to the regulation of microRNA (miRNA) expression. Therefore, changing the profile of miRNAs with the use of natural products is very important in cancer treatment. However, the role of vulpinic acid and related miRNAs in breast cancer progression remains unknown. Vulpinic acid, methyl (as2E)-2-(3-hydroxy-5-oxo-4-phenylfuran-2-ylidene)-2 phenylacetate, is a natural product extracted from the lichen species and shows an anticancer effect on different cancer cells. Methods This study examines the effects of vulpinic acid on the miRNA levels of breast cancer (MCF-7) cells and its relationship with cell proliferation and apoptosis levels. The antiproliferative effect of vulpinic acid was screened against MCF-7 breast cancer cells and MCF-12A breast epithelial cells using the xCELLigence real-time cell analysis system. We analyzed the altered miRNA expression profile in MCF-7 breast cancer cells versus MCF-12A cells following their response to vulpinic acid through microarray analysis. The microarray analysis results were confirmed through quantitative real-time PCR and bioinformatics analysis. Results The results of the miRNA array and bioinformatic analyses demonstrated that 12 miRNAs were specifically responsive to vulpinic acid in MCF-7 breast cancer cells. This is the first study to reveal that vulpinic acid inhibits the expression of 12 miRNAs and suppresses breast cancer cell proliferation. The study also revealed that vulpinic acid may downregulate the expression of 12 miRNAs by repressing the FOXO-3 gene. The miRNA targets were mainly found to play a role in the apoptosis, cell cycle and MAPK pathways. Moreover, Bcl-2, Bax, procaspase-3 and procaspase-9 protein levels were assessed by western blot analysis for validation of apoptosis at the protein level. Conclusion This study revealed the molecular mechanisms of vulpinic acid on breast cancer and showed that vulpinic acid regulates apoptosis signaling pathways by decreasing the expression of miRNAs. The miRNA expression patterns illuminate the underlying effect of vulpinic acid in breast cancer treatment. Graphical Abstract
format	article
author	Demet Cansaran-Duman Sevcan Yangın Betül Çolak
author_facet	Demet Cansaran-Duman Sevcan Yangın Betül Çolak
author_sort	Demet Cansaran-Duman
title	The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
title_short	The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
title_full	The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
title_fullStr	The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
title_full_unstemmed	The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
title_sort	role of vulpinic acid as a natural compound in the regulation of breast cancer-associated mirnas
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c87fb5c02321453da990fc01d86ca411
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The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs

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