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


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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.

About the authors

Shengping Zhai

Department of General Practice, Yantai Yuhuangding Hospital Affiliated to Qingdao University

Email: info@benthamscience.net

Xiaoping Li

Department of Pulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital Affiliated to Qingdao University

Email: info@benthamscience.net

Tiantian Lin

Respiratory Intensive Care Unit, Yantai Yuhuangding Hospital Affiliated to Qingdao University

Author for correspondence.
Email: info@benthamscience.net

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