J 2024

MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B

JONAS, Katharina, Felix PRINZ, Manuela FERRACIN, Katarina KRAJINA, Alexander DEUTSCH et. al.

Basic information

Original name

MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B

Authors

JONAS, Katharina, Felix PRINZ, Manuela FERRACIN, Katarina KRAJINA, Alexander DEUTSCH, Tobias MADL, Beate RINNER, Ondřej SLABÝ, Christiane KLEC and Martin PICHLER

Edition

Non-coding RNA, Švýcarsko, MDPI, 2024, 2311-553X

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

Switzerland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Lékařská fakulta – Repository – Repository

DOI

http://dx.doi.org/10.3390/ncrna10010002

UT WoS

001170546900001

Keywords in English

microRNA (miRNA); triple negative breast cancer (TNBC); cholesterol transport protein; GRAM domain-containing protein 1B (GRAMD1B)

Links

LX22NPO5102, research and development project.
Changed: 12/6/2024 04:49, RNDr. Daniel Jakubík

Abstract

V originále

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.
Displayed: 10/5/2025 07:16