microRNA-130b-3p contained in MSC-derived EVs promotes lung cancer progression by regulating the FOXO3/NFE2L2/TXNRD1 axis
| Autor: | Sui Zesen, Kaican Cai, Jianhua Zhang, Yijun Mo, Li Dongfang, Chenghua Zhong, Jianfeng Tan, Jun Kuang, Tieniu Song, Jun Yan, Quanwei Guo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Keap1 Cancer Research Biology lcsh:RC254-282 Flow cytometry 03 medical and health sciences 0302 clinical medicine TXNRD1 microRNA medicine Gene silencing Pharmacology (medical) Lung cancer NFE2L2 mesenchymal stem cells medicine.diagnostic_test Cell growth microRNA-130b-3p Mesenchymal stem cell FOXO3 Transfection lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease lung cancer 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article extracellular vesicles |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 20, Iss, Pp 132-146 (2021) |
| ISSN: | 2372-7705 |
| Popis: | This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression in vivo. miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression in vivo. In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression. Graphical Abstract The study mainly addresses the oncogenic role of miR-130b-3p contained in mesenchymal stem cell-derived extracellular vesicles in the malignant progression of lung cancer, which was associated with the FOXO3/NFE2L2/TXNRD1 axis, thus highlighting a potential therapeutic action against lung cancer. |
| Databáze: | OpenAIRE |
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