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microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner

Cancer Gene Therapy volume 28, pages 250–264 (2021)Cite this article

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A Correction to this article was published on 01 December 2021

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Abstract

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of serum-derived exosomal miR-let-7e as a biomarker in the metastasis of NSCLC. Initially, the expression of miR-let-7e, SUV39H2, and CDH1 in human NSCLC tissues and exosomes isolated from the serum of NSCLC patients was determined by RT-qPCR, demonstrating that miR-let-7e was downregulated in NSCLC tissues and serum-derived exosomes, while SUV39H2 was upregulated in NSCLC tissues. Kaplan–Meier method revealed that both lower miR-let-7e expression and higher SUV39H2 expression were correlated with a lower survival rate of NSCLC patients. Next, SUV39H2 was predicted and validated to be a target of miR-let-7e using dual-luciferase reporter assay. NSCLC H1299 cells following ectopic expression and depletion experiments of miR-let-7e and SUV39H2 were treated with serum-derived exosomes, after which the viability, migration, and invasion of H1299 cells were detected using CCK-8 and Transwell assays. Further, in vivo experiments were conducted to elucidate the effect of exosomal miR-let-7e on tumorigenesis. Results revealed that miR-let-7e overexpression in serum-derived exosomes inhibited SUV39H2, resulting in impaired cell viability, migration, and invasion in vitro as well as delayed tumor growth in vivo. In conclusion, the key findings of the current study demonstrate that exosomal miR-let-7e from serum possesses anticarcinogenic properties against NSCLC via the SUV39H2/LSD1/CDH1 axis.

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Fig. 1: The significance of let-7e, SUV39H2, LSD1, and CDH1 in the NSCLC development.
Fig. 2: Serum exosomes of NSCLC patients stimulate NSCLC viability, migration, and invasion.
Fig. 3: Poor miR-let-7e expression correlates to with the low survival of NSCLC patients.
Fig. 4: Abundant expression of SUV39H2/LSD1 is associated with poor survival rate of NSCLC patients.
Fig. 5: LSD1 reduces CDH1 expression via regulating CDH1 promoter demethylation.
Fig. 6: MiR-let-7e in the exosomes attenuates NSCLC cell viability, migration, and invasion via mediation of the SUV39H2/LSD1/CDH1 axis.
Fig. 7: miR-let-7e in the exosomes retards tumor growth and metastasis in vivo.
Fig. 8: The mechanism graph of the regulatory role of miR-let-7e in the exosomes via the SUV39H2/LSD1/CDH1 axis in NSCLC.

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Acknowledgements

The authors would like to acknowledge the helpful comments on this paper received from the reviewers.

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Authors and Affiliations

  1. Department of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China

    Shufeng Xu

  2. Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China

    Lei Zheng, Hongmei Xu & Liming Gao

  3. Department of Oncology, Tianjin Wuqing District People’s Hospital, Tianjin, 301700, PR China

    Liying Kang

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Contributions

L.G. and S.X. designed the study. L.Z. and L.K. collated the data, carried out data analyses, and produced the initial draft of the manuscript. L.G. and H.X. contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Liming Gao.

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Xu, S., Zheng, L., Kang, L. et al. microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner. Cancer Gene Ther 28, 250–264 (2021). https://doi.org/10.1038/s41417-020-00216-1

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