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Updated: Nov 2, 2025
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7
Margherita Piccolella1, Riccardo Cristofani1, Barbara Tedesco1,2
1Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Milan, Italy.
Abstract:
Breast cancer (BC) is a serious and widespread disease for which different treatments have been developed. In addition to the classic therapies, the treatment with retinoic acid (RA) is still being clinically investigated. RA reduces cancer cells proliferation and migration, but its molecular mechanism of action is not clear. In tumor development, autophagy promotes cancer cell survival and prevents apoptosis. Small heat shock protein B8 (HSPB8) acts together with its co-chaperone BCL-2 associated athanogene 3 (BAG3) stimulating BC proliferation and migration. We analyzed whether direct correlations exist between RA and HSPB8 or BAG3 and how this may play a role in BC. We measured HSPB8 and BAG3 gene expression in MCF-7 BC cells and we analyzed the potential correlation between the antiproliferative and antimigratory effect of RA with the expression level of HSPB8. We found that in MCF-7 cells RA reduces both HSPB8 and BAG3 gene expression and it alters the mitotic spindle organization. Notably, the effects of RA on HSPB8 levels are exerted at both transcriptional and translational levels. RA effects are possibly mediated by miR-574-5p that targets the HSPB8 transcript. Our results suggest that therapeutic doses of RA can efficiently counteract the adverse effects of HSPB8 in BC progression.
Insights
Retinoic acid (RA) treatment reduces breast cancer (BC) cell proliferation and migration by decreasing HSPB8 and BAG3 gene expression. RA also impacts mitotic spindle organization, suggesting a potential therapeutic role in BC progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Breast cancer (BC) is a prevalent disease with ongoing research into novel therapeutic strategies.
- Retinoic acid (RA) shows promise in reducing cancer cell proliferation and migration, but its precise molecular mechanisms in BC remain unclear.
- Autophagy and the HSPB8/BAG3 complex are implicated in promoting cancer cell survival and proliferation in BC.
Purpose of the Study:
- To investigate the correlation between retinoic acid (RA) and the expression of HSPB8 and BAG3 in breast cancer (BC).
- To elucidate the molecular mechanisms by which RA influences BC progression, focusing on HSPB8 and BAG3.
- To assess the potential of RA as a therapeutic agent to counteract HSPB8-mediated adverse effects in BC.
Main Methods:
- Gene expression analysis of HSPB8 and BAG3 in MCF-7 BC cells treated with RA.
- Assessment of the correlation between RA's antiproliferative/antimigratory effects and HSPB8 expression levels.
- Investigation of RA's impact on mitotic spindle organization and HSPB8 regulation at transcriptional and translational levels.
Main Results:
- RA treatment significantly reduced both HSPB8 and BAG3 gene expression in MCF-7 cells.
- RA altered the mitotic spindle organization in BC cells.
- RA's effects on HSPB8 were observed at both transcriptional and translational levels, potentially mediated by miR-574-5p.
- RA demonstrated the ability to counteract the pro-proliferative effects of HSPB8.
Conclusions:
- Retinoic acid (RA) effectively downregulates HSPB8 and BAG3 expression in breast cancer cells.
- RA influences key cellular processes like mitotic spindle organization, offering a potential therapeutic avenue.
- These findings suggest RA can mitigate the negative impact of HSPB8 on BC progression, highlighting its therapeutic potential.
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