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Extracellular Vesicles-Encapsulated miR-153-3p Potentiate the Survival and Invasion of Lung Adenocarcinoma

  • Cao, Hongli (Department of Respiratory, Beijing Rehabilitation Hospital, Capital Medical University) ;
  • Zhang, Ping (Department of Respiratory, Beijing Rehabilitation Hospital, Capital Medical University) ;
  • Yu, Hong (Department of Respiratory, Beijing Rehabilitation Hospital, Capital Medical University) ;
  • Xi, Jianing (Department of Respiratory, Beijing Rehabilitation Hospital, Capital Medical University)
  • Received : 2021.08.21
  • Accepted : 2022.01.14
  • Published : 2022.06.30

Abstract

Extracellular vesicles (EVs) play an essential role in the communication between cells and the tumor microenvironment. However, the effect of tumor-derived EVs on the growth and metastasis of lung adenocarcinoma (LUAD) remains to be explored. This study aimed to elucidate the role of miR-153-3p-EVs in the invasion and migration capabilities of LUAD cells and explore its mechanism through in vivo and in vitro experiments. We found that miR-153-3p was specifically and highly expressed in LUAD and its secreted EVs. Furthermore, the expression of BANCR was negatively regulated by miR-153-3p and identified as a target gene of miR-153-3p using luciferase reporter assays. Through further investigation, we found that the downregulation of BANCR activates the PI3K/AKT pathway and accelerates the process of epithelial-mesenchymal transition (EMT), which ultimately leads to the aggravation of LUAD. The orthotopic xenograft mouse model was established to illustrate the effect of miR-153-3p-EVs on LUAD. Animal studies showed that miR-153-3p-EVs accelerated tumor growth in mice. Besides, we found that miR-153-3p-EVs could damage the respiratory ability of mice and produce a mass of inflammatory cells around the lung tissue of mice. Nevertheless, antagomir-153-3p treatment could inhibit the deterioration of respiratory function and inhibit the growth of lung tumors in mice. In conclusion, our study reveals the potential molecular mechanism of miR-153-3p-EVs in the development of LUAD and provides a potential strategy for the treatment of LUAD.

Keywords

Acknowledgement

This work was supported by the Science and Technology Development Special Project of Beijing Rehabilitation Hospital Affiliated to Capital Medical University (2019-002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We greatly appreciate the support from the Beijing Rehabilitation Hospital.

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