Neural Stem Cell‑derived Exosomes Transfer MiR‑124‑3p into Cells to Inhibit Glioma Growth by Targeting FLOT2

Overview

Journal Int J Oncol

Specialty Oncology

Date 2022 Aug 5

PMID 35929514

Authors

Cheng Qian

You Wang

Yunxiang Ji

Danmin Chen

Chuanfang Wang

Guilong Zhang

Yezhong Wang

Affiliations

Soon will be listed here.

Abstract

Currently, exosomes (EXOs) are being explored as novel drug delivery carriers with greater advantages, including crossing the blood‑brain‑barrier and loading drugs. The present study utilized EXOs derived from neural stem cells (NSCs) for the delivery of molecular drugs to treat gliomas. was selected according to previous studies by the authors, and the effects of the delivery of miR‑124‑3p to glioma cells by NSC‑EXOs and were evaluated. It was found that NSC‑EXOs successfully delivered miR‑124‑3p into glioma cells, and NSC‑EXOs loaded with miR‑124‑3p significantly inhibited glioma cell proliferation, invasion and migration. Furthermore, the delivery of miR‑124‑3p by NSC‑EXOs suppressed flotillin 2 (FLOT2) expression by specifically binding to the 3' untranslated region of the gene in gliomas; subsequently, AKT1 was found to be associated with the EXO‑miR‑124‑3p/FLOT2 pathway. Moreover, the therapeutic effects of the delivery of miR‑124‑3p by NSC‑EXOs were confirmed in a mouse tumor xenograft model of glioma. Thus, bio‑carrier NSC‑EXOs loaded with miR‑124‑3p suppressed glioma growth via the EXO‑miR‑124‑3p/ pathway. On the whole, the present study provides insight into stem cell‑free molecular‑targeted therapy based on bio‑carrier NSC‑EXOs and provides a potential strategy for the treatment of glioma.

Citing Articles

Utilization of nanotechnology to surmount the blood-brain barrier in disorders of the central nervous system.

Luo Q, Yang J, Yang M, Wang Y, Liu Y, Liu J Mater Today Bio. 2025; 31:101457.

PMID: 39896289 PMC: 11786670. DOI: 10.1016/j.mtbio.2025.101457.

Ginsenoside Rg1 Regulates the Activation of Astrocytes Through lncRNA-Malat1/miR-124-3p/Lamc1 Axis Driving PI3K/AKT Signaling Pathway, Promoting the Repair of Spinal Cord Injury.

Zhu Y, Zou W, Sun B, Shen K, Xia F, Wang H CNS Neurosci Ther. 2024; 30(11):e70103.

PMID: 39491316 PMC: 11532020. DOI: 10.1111/cns.70103.

Advances in different adult stem cell-derived exosomal non-coding RNAs for the treatment of neurological disorders: a narrative review.

Ke L, Cao Y, Lu Z, Hallajzadeh J Front Cell Dev Biol. 2024; 12:1459246.

PMID: 39450275 PMC: 11500198. DOI: 10.3389/fcell.2024.1459246.

Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes.

Wang Y, Li Q, Zhou S, Tan P Front Endocrinol (Lausanne). 2024; 15:1374715.

PMID: 39220365 PMC: 11361949. DOI: 10.3389/fendo.2024.1374715.

The role and application of small extracellular vesicles in glioma.

Yang Z, Wu H, Wang Z, Bian E, Zhao B Cancer Cell Int. 2024; 24(1):229.

PMID: 38951882 PMC: 11218314. DOI: 10.1186/s12935-024-03389-z.

References

Wu H, Mu X, Liu L, Wu H, Hu X, Chen L . Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1. Cell Death Dis. 2020; 11(9):801. PMC: 7519084. DOI: 10.1038/s41419-020-02962-4. View

Zhang G, Chen L, Khan A, Li B, Gu B, Lin F . miRNA-124-3p/neuropilin-1(NRP-1) axis plays an important role in mediating glioblastoma growth and angiogenesis. Int J Cancer. 2018; 143(3):635-644. DOI: 10.1002/ijc.31329. View

Zeng Z, Li Y, Pan Y, Lan X, Song F, Sun J . Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun. 2018; 9(1):5395. PMC: 6300604. DOI: 10.1038/s41467-018-07810-w. View

Wang X, Yang Q, Guo L, Li X, Zhao X, Song L . Flotillin-2 is associated with breast cancer progression and poor survival outcomes. J Transl Med. 2013; 11:190. PMC: 3765773. DOI: 10.1186/1479-5876-11-190. View

Zhang G, Zhu Z, Wang H, Yu Y, Chen W, Waqas A . Exosomes derived from human neural stem cells stimulated by interferon gamma improve therapeutic ability in ischemic stroke model. J Adv Res. 2020; 24:435-445. PMC: 7289755. DOI: 10.1016/j.jare.2020.05.017. View

Guo S, Chen J, Chen F, Zeng Q, Liu W, Zhang G . Exosomes derived from -infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16. Gut. 2020; . DOI: 10.1136/gutjnl-2020-321187. View

Qin E, Cooper D, Abbott K, Lennon J, Nagaraja S, Mackay A . Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma. Cell. 2017; 170(5):845-859.e19. PMC: 5587159. DOI: 10.1016/j.cell.2017.07.016. View

Hoxhaj G, Manning B . The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 2019; 20(2):74-88. PMC: 7314312. DOI: 10.1038/s41568-019-0216-7. View

Marban E . The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics. J Am Coll Cardiol. 2018; 71(2):193-200. PMC: 5769161. DOI: 10.1016/j.jacc.2017.11.013. View

10.

Katakowski M, Chopp M . Exosomes as Tools to Suppress Primary Brain Tumor. Cell Mol Neurobiol. 2016; 36(3):343-52. PMC: 11482504. DOI: 10.1007/s10571-015-0280-9. View

11.

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

12.

Hazarika P, McCarty M, Prieto V, George S, Babu D, Koul D . Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res. 2004; 64(20):7361-9. DOI: 10.1158/0008-5472.CAN-04-0823. View

13.

Bond A, Ming G, Song H . Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later. Cell Stem Cell. 2015; 17(4):385-95. PMC: 4683085. DOI: 10.1016/j.stem.2015.09.003. View

14.

Reifenberger G, Wirsching H, Knobbe-Thomsen C, Weller M . Advances in the molecular genetics of gliomas - implications for classification and therapy. Nat Rev Clin Oncol. 2016; 14(7):434-452. DOI: 10.1038/nrclinonc.2016.204. View

15.

Saadatpour L, Fadaee E, Fadaei S, Nassiri Mansour R, Mohammadi M, Mousavi S . Glioblastoma: exosome and microRNA as novel diagnosis biomarkers. Cancer Gene Ther. 2016; 23(12):415-418. DOI: 10.1038/cgt.2016.48. View

16.

Mutukula N, Elkabetz Y . "Neural Killer" Cells: Autologous Cytotoxic Neural Stem Cells for Fighting Glioma. Cell Stem Cell. 2017; 20(4):426-428. DOI: 10.1016/j.stem.2017.03.019. View

17.

Zhang G, Chen L, Guo X, Wang H, Chen W, Wu G . Comparative Analysis of microRNA Expression Profiles of Exosomes Derived from Normal and Hypoxic Preconditioning Human Neural Stem Cells by Next Generation Sequencing. J Biomed Nanotechnol. 2018; 14(6):1075-1089. DOI: 10.1166/jbn.2018.2567. View

18.

LaPointe S, Perry A, Butowski N . Primary brain tumours in adults. Lancet. 2018; 392(10145):432-446. DOI: 10.1016/S0140-6736(18)30990-5. View

19.

Wang J, Liu J, Sun G, Meng H, Wang J, Guan Y . Glioblastoma extracellular vesicles induce the tumour-promoting transformation of neural stem cells. Cancer Lett. 2019; 466:1-12. DOI: 10.1016/j.canlet.2019.09.004. View

20.

Huang S, Xue P, Han X, Zhang C, Yang L, Liu L . Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis. Cell Death Dis. 2020; 11(6):408. PMC: 7264172. DOI: 10.1038/s41419-020-2621-y. View