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Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI

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Abstract

Background

Tumor hypoxia is a feature of tumor micro-environment (TME), which provides a suitable environment for tumor cells migration and invasion. However, up to now, the function of exosomes derived from hypoxic tumor cells is still not fully understood. The present study is aimed to explore the underlying mechanisms of lung cancer-secreted exosomes-mediated tumor metastasis under hypoxia.

Methods & Results

Exosomes were isolated from normoxic or hypoxic NCI-H446 cells. Some characteristic proteins were detected by western blots. Levels of CD63, CD 9 and CD 81 proteins were up-regulated on the membrane of exosomes secreted by hypoxic NCI-H446 cells. Basing on the results from miRNA sequencing, qRT-PCR and wound healing assay, hsa-miR-625-3p was discovered to be accumulated inside hypoxic exosomes and responsible for the metastasis of lung cancer cell. Further experiments from luciferase reporter gene assay demonstrated hsa-miR-625-3p could directly inhibit SCAI expression through binding with its 3’UTR, which suggested the mechanisms by which exosomal hsa-miR-625-3p suppressed tumor cells migration.

Conclusions

Exosomal miR-625-3p derived from hypoxic small lung cancer cells accelerated tumor cells migration through inhibiting SCAI directly.

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Abbreviations

SCLC:

small cell lung cancer.

TME:

tumor micro-environment.

NTA:

nanoparticle tracking analysis.

PCR:

polymerase chain reaction.

EMT:

epithelia–mesenchymal transition.

MAP2K6:

mitogen-activated protein kinase kinase 6.

SCAI:

suppressor of cancer cell invasion.

LTBP3:

latent TGFβ binding protein 3.

SNED1:

sushi, nidogen and EGF-like domains 1.

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Acknowledgements

This study was supported in part by the grant from Beijing Hospitals Authority (XMLX201702).

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Authors and Affiliations

  1. Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, PR China

    Yi Zhang, Kun Qian, Xingsheng Liu, Xin Zhao, Teng Zhao & Gaojun Lu

Authors
  1. Yi Zhang
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  2. Kun Qian
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  3. Xingsheng Liu
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  4. Xin Zhao
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  5. Teng Zhao
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  6. Gaojun Lu
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Contributions

Yi Zhang contributed to the design of the experiment and writing the main manuscript. Kun Qian contributed to literature search and finishing the experiment, such as transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), flow cytometry, western blotting analysis and real-time reverse transcription polymerase chain reaction (RT-PCR). Xingsheng Liu contributed to data analysis and data interpretation. Teng Zhao contributed to the experimental data collection. Gaojun Lu contributed to writing the abstract.

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Correspondence to Yi Zhang.

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Zhang, Y., Qian, K., Liu, X. et al. Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI. Mol Biol Rep 49, 9275–9281 (2022). https://doi.org/10.1007/s11033-022-07763-w

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  • DOI: https://doi.org/10.1007/s11033-022-07763-w

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