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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Obese Mouse Fat Cell-derived Extracellular Vesicles Transport miR-99a-5p to Mitigate the Proliferation and Migration of Non-small Cell Lung Cancer Cells

Author(s): Shengping Zhai, Xiaoping Li and Tiantian Lin*

Volume 27, Issue 2, 2024

Published on: 12 June, 2023

Page: [214 - 226] Pages: 13

DOI: 10.2174/1386207326666230316103604

Price: $65

Abstract

Objective: Fat cells-derived extracellular vesicles (FC-EVs) play a role in regulating the tumor microenvironment in cancers by transporting RNAs. MicroRNAs (miRNAs) are vital regulators of cancer development. This study was conducted to explore the role of FC-EVs in the proliferation and migration of non-small cell lung cancer (NSCLC) cells, providing targets for NSCLC treatment.

Methods: The obese mouse model was established via high‐fat diet (HFD), followed by separation and characterization of FC-EVs (HFD-EVs). The levels of miR-99a-5p, precursor-miR-99a-5p, and heparan sulfate-glucosamine 3-sulfotransferase 3B1 (HS3ST3B1) were measured by RT-qPCR or Western blot assay. Cell proliferation and migration were evaluated by 3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide and wound healing assays. The expression of Cy3-labeled miR-99a-5p in A549 cells (one NSCLC cell line) was observed via confocal microscopy. The binding of miR-99a-5p to HS3ST3B1 was analyzed by the dual luciferase assay. Rescue experiments were performed to confirm the role of HS3ST3B1 in NSCLC cells.

Results: miR-99a-5p was upregulated in adipose tissues, FCs, and HFD-EVs. HFD-EVs mitigated the proliferation and migration of NSCLC cells. HFD-EVs transported miR-99a-5p into A549 cells, which upregulated miR-99a-5p expression and inhibited HS3ST3B1 expression in A549 cells. HS3ST3B1 overexpression reversed the inhibition of HFD-EVs on the proliferation and migration of NSCLC cells.

Conclusion: HFD-EVs transported miR-99a-5p into NSCLC cells and inhibited HS3ST3B1, thereby inhibiting proliferation and migration of NSCLC cells.

Keywords: Non-small cell lung cancer, obesity, fat cells, extracellular vesicles, miR-99a-5p, HS3ST3B1.

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