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Restored microRNA-519a enhances the radiosensitivity of non-small cell lung cancer via suppressing EphA2

Gene Therapy volume 29, pages 588–600 (2022)Cite this article

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Abstract

Accumulating evidence has demonstrated that microRNA-519a (miR-519a) acts as the tumor suppressor in various cancers, but little is known regarding its intrinsic regulatory mechanisms in non-small cell lung cancer (NSCLC). Here, we aimed to investigate the role of miR-519a-targeted ephrinA2 receptor (EphA2) in radiosensitivity of NSCLC. MiR-519a and EphA2 expression in NSCLC and paracancerous tissues were detected using RT-qPCR and western blot analysis. A549 cell line was cultured and radiation-resistant cell line A549R was constructed using fractionated X-ray irradiation of these cells at 60 Gy. Colony formation ability and radioresistance of parent strain A549 and resistant strain A549R were detected with restored miR-519a and depleted EphA2. MTT assay was used to measure cell proliferation, flow cytometry was performed for determination of cell cycle distribution and apoptosis. The migration and invasion abilities were assessed by Transwell assay. The target relationship between miR-519a and EphA2 was verified. Results suggested that miR-519a was downregulated and EphA2 was upregulated in NSCLC tissues and cells, and miR-519a targeted EphA2. MiR-519a expression declined, while EphA2 expression elevated in A549R cells versus A549 cells. Upregulated miR-519a and downregulated EphA2 suppressed D0, Dq, survival fraction (SF2) and N-value, arrested cells at G0/G1 phase, advanced the apoptosis and attenuated migration, proliferation, and invasion of A549 and A549R cells. Overexpression of EphA2 reversed the promotion of upregulated miR-519a on radiosensitivity of NSCLC cells. Our results revealed that miR-519a enhances radiosensitivity of NSCLC by inhibiting EphA2 expression. Moreover, miR-519a serves as a target for NSCLC treatment.

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Fig. 1: MiR-519a decreased and EphA2 increased in NSCLC tissues.
Fig. 2: Radiosensitivity of the parental A549 and radioresistant A549R cell lines.
Fig. 3: MiR-519a expression is lower, while EphA2 expression is higher in A549R cells than A549 cells; EphA2 is a target gene of miR-519a.
Fig. 4: Highly expressed miR-519a and lowly expressed EphA2 enhance the radiosensitivity of A549 and A549R cells.
Fig. 5: Upregulated miR-519a and downregulated EphA2 advance the apoptosis and attenuate the proliferation of A549 and A549R cells.
Fig. 6: Restored miR-519a and depleted EphA2 reduce invasion and migration ability of A549 and A549R cells.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

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  1. Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Shulei Gong, Yu Li, Ling Lv & Wanfu Men

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  1. Shulei Gong
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Correspondence to Wanfu Men.

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The study was endorsed by the Institutional Review Board of the first affiliated hospital of China medical university. All participants signed a document of informed consent.

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Gong, S., Li, Y., Lv, L. et al. Restored microRNA-519a enhances the radiosensitivity of non-small cell lung cancer via suppressing EphA2. Gene Ther 29, 588–600 (2022). https://doi.org/10.1038/s41434-020-00213-x

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