Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1

Tumor-derived exosomes are highly correlated with tumor progression and angiogenesis. This study was designed to probe the role of tumor-derived exosomal miR-1247-3p in mediating the angiogenesis in bladder cancer. Exosomes isolation from the culture medium of normal or bladder cancer cell lines was performed using a differential centrifugation method. miR-1247-3p expression in exosomes and cells was detected by quantitative real-time PCR (qRT-PCR). The effect of exosomes on the angiogenesis of human umbilical vein endothelial cells (HUVECs) was assessed using cell counting kit-8 (CCK-8), transwell and tube formation assays. The interaction between miR-1247-3p and forkhead box protein O1 (FOXO1) was studied using luciferase reporter and RNA pull down assays. Exosomes were successfully isolated from T24, UM-UC-3, and SV-HUC-1 cells, as confirmed by corresponding identifications. Functional experiments revealed that exosomes derived from T24 and UM-UC-3 cells significantly enhanced the abilities of proliferation, migration, angiogenesis, and vascular endothelial-derived growth factor (VEGF) secretion in HUVECs. miR-1247-3p was highly expressed in exosomes derived from T24 and UM-UC-3 cells, and exosomes derived from miR-1247-3p inhibitor-transfected cells reduced HUVEC viability, migration, tube formation, and VEGF level. FOXO1 was confirmed as a direct target of miR-1247-3p. Rescue assays suggested that the effect of miR-1247-3p inhibition on the viability, migration, and angiogenesis of HUVECs was partly abrogated by the knockdown of FOXO1. Our data suggest that miR-1247-3p is up-regulated in tumor-derived exosomes, thereby inhibiting FOXO1 expression and facilitating angiogenesis in bladder cancer.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Cancer biology & therapy - 25(2024), 1 vom: 31. März, Seite 2290033

Sprache:

Englisch

Beteiligte Personen:

Liu, Zonglai [VerfasserIn]
Du, Dan [VerfasserIn]
Zhang, Shizhong [VerfasserIn]

Links:

Volltext

Themen:

Angiogenesis
Bladder cancer
Exosomes
FOXO1
FOXO1 protein, human
Forkhead Box Protein O1
Journal Article
MIRN1247 microRNA, human
MiR-1247-3p
MicroRNAs
Vascular Endothelial Growth Factor A

Anmerkungen:

Date Completed 16.12.2023

Date Revised 11.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/15384047.2023.2290033

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365638528