NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma

© 2024. The Author(s)..

It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Scientific reports - 14(2024), 1 vom: 24. März, Seite 6979

Sprache:

Englisch

Beteiligte Personen:

Zhang, Pingping [VerfasserIn]
Wang, Qun [VerfasserIn]
Lu, Weijun [VerfasserIn]
Zhang, Feng [VerfasserIn]
Wu, Dongde [VerfasserIn]
Sun, Junwei [VerfasserIn]

Links:

Volltext

Themen:

CAFs-derived exosomes
Glucose
Glucose metabolism
HIF-1α
HIF1A protein, human
IY9XDZ35W2
Journal Article
MIRN889 microRNA, human
MiR-889-3p
MicroRNAs
NNT-AS1
PDAC
RNA, Antisense

Anmerkungen:

Date Completed 25.03.2024

Date Revised 17.04.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-024-57769-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370114493