TY - JOUR
AU - Sumer, Oyku Ece
AU - Schelzig, Korbinian
AU - Jung, Janine
AU - Li, Xiaoya
AU - Moros, Janina
AU - Schwarzmüller, Luisa
AU - Sen, Ezgi
AU - Karolus, Sabine
AU - Wörner, Angelika
AU - de Melo Costa, Verônica Rodrigues
AU - Nataraj, Nishanth Belugali
AU - Vlachavas, Efstathios-Iason
AU - Gerhäuser, Clarissa
AU - Müller-Decker, Karin
AU - Helm, Dominic
AU - Yarden, Yosef
AU - Michels, Birgitta Elisabeth
AU - Körner, Cindy
TI - Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness.
JO - BMC biology
VL - 23
IS - 1
SN - 1741-7007
CY - Heidelberg
PB - Springer
M1 - DKFZ-2025-00220
SP - 25
PY - 2025
N1 - #EA:B050#LA:B050#
AB - Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet.Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism.In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species.
KW - MicroRNAs: genetics
KW - MicroRNAs: metabolism
KW - Breast Neoplasms: genetics
KW - Breast Neoplasms: pathology
KW - Humans
KW - Female
KW - Neovascularization, Pathologic: genetics
KW - Animals
KW - Cell Line, Tumor
KW - Mice
KW - Gene Expression Regulation, Neoplastic
KW - Angiogenesis
KW - Angiogenesis (Other)
KW - Breast cancer (Other)
KW - IsomiRs (Other)
KW - Metastasis (Other)
KW - Selective arm-usage of miRNA (Other)
KW - miR-1307 (Other)
KW - miRNA arm switch (Other)
KW - miRNAs (Other)
KW - MicroRNAs (NLM Chemicals)
KW - MIRN1307 microRNA, human (NLM Chemicals)
LB - PUB:(DE-HGF)16
C6 - pmid:39849498
C2 - pmc:PMC11756181
DO - DOI:10.1186/s12915-025-02133-x
UR - https://inrepo02.dkfz.de/record/298213
ER -