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MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B
K. Jonas, F. Prinz, M. Ferracin, K. Krajina, A. Deutsch, T. Madl, B. Rinner, O. Slaby, C. Klec, M. Pichler
Status neindexováno Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
DK-MCD W1226
FWF Austrian Science Fund
LX22NPO5102
National Institute for Cancer Research, Next Generation EU, EXCELES
Hertha-Firnberg project
FWF Austrian Science Fund
Scholarship
Austrian Society of Hemato-Oncology (ÖGHO)
NLK
Directory of Open Access Journals
od 2015
PubMed Central
od 2015
Europe PubMed Central
od 2015
ProQuest Central
od 2015-06-01
Open Access Digital Library
od 2015-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2015
PubMed
38250802
DOI
10.3390/ncrna10010002
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC.
BioTechMed Graz 8010 Graz Austria
Department for Biomedical Research Medical University of Graz 8036 Graz Austria
Department of Medical and Surgical Sciences University of Bologna 40126 Bologna Italy
Division of Hematology Department of Internal Medicine Medical University of Graz 8036 Graz Austria
Division of Oncology Department of Internal Medicine Medical University of Graz 8036 Graz Austria
Research Unit for Non Coding RNA and Genome Editing Medical University of Graz 8010 Graz Austria
Translational Oncology 2 Med Clinics Hematology and Oncology 86156 Augsburg Germany
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- $a MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC.
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