Mesenchymal stem cell-derived extracellular vesicles alleviate cervical cancer by delivering microRNA-331-3p to reduce LIM zinc finger domain containing 2 methylation in tumor cells.

Abstract

The aim of this study is to investigate if extracellular vesicles (EVs) from bone marrow mesenchymal stem cells (BMSCs) deliver microRNA (miR)-331-3p to regulate LIM zinc finger domain containing 2 (LIMS2) methylation in cervical cancer cells. Cervical cancer cells were incubated with EVs from BMSCs with altered expression of miR-331-3p, DNA methyltransferase 3 alpha (DNMT3A) or/and LIMS2 and then subjected to 5-ethynyl-2'-deoxyuridine, Transwell, flow cytometry and western blotting analyses. Dual-luciferase reporter assay was conducted to verify the binding between miR-331-3p and DNMT3A. A xenograft model was established to evaluate the effect of BMSC-derived EV-miR-331-3p on cervical tumor growth. miR-331-3p was lowly and DNMT3A was highly expressed in cervical cancer. BMSC-derived EVs delivered miR-331-3p to control the behaviors of cervical cancer cells. miR-331-3p inhibited the expression of DNMT3A by binding DNMT3A mRNA. DNMT3A promoted LIMS2 methylation and reduced the expression of LIMS2. Overexpression of DNMT3A or silencing of LIMS2 in BMSCs counteracted the tumor suppressive effects of miR-331-3p. BMSC-derived EV-miR-331-3p also inhibited the growth of cervical tumors in vivo. BMSC-derived EVs alleviate cervical cancer partially by delivering miR-331-3p to reduce DNMT3A-dependent LIMS2 methylation in tumor cells.

• Authors: Shanshan Yang, Le Wang, Lina Gu, Zhao Wang, Yuan Wang, Jianan Wang, Yunyan Zhang
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 31 Issue 22 Pg. 3829-3845 (11 10 2022) ISSN: 1460-2083 [Electronic] England
• PMID: 35708510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• DNA (Cytosine-5-)-Methyltransferases
• MicroRNAs
• DNA Methyltransferase 3A
• MIRN331 microRNA, human

Topics

• Female
• Humans
• Uterine Cervical Neoplasms (genetics)
• DNA (Cytosine-5-)-Methyltransferases (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• Mesenchymal Stem Cells (metabolism)
• DNA Methylation (genetics)
• Extracellular Vesicles (genetics, metabolism)
• DNA Methyltransferase 3A
• Zinc Fingers