MicroRNA-302a-3p induces ferroptosis of non-small cell lung cancer cells via targeting ferroportin

Ferroptosis is a newly described regulated form of cell death that contributes to the progression of non-small cell lung cancers (NSCLCs). MicroRNA-302a-3p (miR-302a-3p) plays critical roles in the tumorigenicity of different cancers; however, its function and underlying mechanism in ferroptosis and...

Full description

Saved in:
Bibliographic Details
Published in:Free radical research 2021-07, Vol.55 (7), p.722-731
Main Authors: Wei, Dong, Ke, Yao-Qi, Duan, Peng, Zhou, Lei, Wang, Chang-Ying, Cao, Ping
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Cation Transport Proteins - antagonists & inhibitors
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Cell Proliferation
ferroportin
Ferroptosis
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
MicroRNAs - genetics
miR-302a-3p
NSCLCs
Tumor Cells, Cultured
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ferroptosis is a newly described regulated form of cell death that contributes to the progression of non-small cell lung cancers (NSCLCs). MicroRNA-302a-3p (miR-302a-3p) plays critical roles in the tumorigenicity of different cancers; however, its function and underlying mechanism in ferroptosis and NSCLCs remain unclear. Human NSCLCs cells were incubated with miR-302a-3pmimic or inhibitor in the presence or absence of erastin or RSL3. Cell viability, colony numbers, lactate dehydrogenase (LDH) releases, lipid peroxidation and intracellular iron level were measured. Besides, the synergistic effects of cisplatin and paclitaxel with miR-302a-3p were determined. miR-302a-3p level was reduced in human NSCLCs cells and tissues. ThemiR-302a-3p mimic induced lipid peroxidation, iron overload and ferroptosis, thereby inhibiting cell growth and colony formation of NSCLCs cells. Conversely, the miR-302a-3p inhibitor block ederastin- or RSL3-related ferroptosis and tumor suppression. Additionally, we found that miR-302a-3p directly bound to the 3′-untranslational region of ferroportin to decrease its protein expression, and that ferroportin overexpression significantly prevented miR-302a-3p mimic-induced ferroptosis and tumor inhibition. Moreover, the miR-302a-3p mimic sensitized NSCLCs cells to cisplatin and paclitaxel chemotherapy. miR-302a-3p functions as a tumor inhibitor, at least partly, via targeting ferroportin to induce ferroptosis of NSCLCs.
ISSN:1071-5762
1029-2470
DOI:10.1080/10715762.2021.1947503