We explored the mechanism by which miR-139 modulates radioresistance of esophageal cancer (EC). The radioresistant cell line KYSE150R was obtained from the parental KYSE150 cell line by fractionated irradiation (15×2 Gy; total dose of 30 Gy). The cell cycle was assessed by flow cytometry. A gene profiling study was conducted to detect the expression of genes related to the radioresistance of EC. In the KYSE150R line, flow cytometry revealed increased number of G1-phase cells and decreased number of G2-phase cells; the expression of miR-139 increased. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. Western blotting showed that miR-139 knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. However, PDK1 inhibitor GSK2334470 reversed this effect for p-AKT and cyclin D1 expression. A luciferase reporter assay indicated that miR-139 directly bound to the PDK1 mRNA 3’-UTR. Analysis of the clinical data from 110 patients with EC showed an association of miR-139 expression with the TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival. In conclusion, miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.
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12 April 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10517-023-05773-7
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 10, pp. 501-508, October, 2022
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Liu, Y., Liu, Y. & Jiao, W.P. MiR-139 Affects Radioresistance in Esophageal Cancer by Targeting the PDK1/AKT/Cyclin D1 Signaling Pathway. Bull Exp Biol Med 174, 489–496 (2023). https://doi.org/10.1007/s10517-023-05735-z
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DOI: https://doi.org/10.1007/s10517-023-05735-z