Acquired radioresistance is one of the main obstacles for the anti-tumour efficacy of radiotherapy in oesophageal cancer (EC). Recent studies have proposed microRNAs (miRNAs) as important participators in the development of radioresistance in various cancers. Here, we investigated the role of miR-1275 in acquired radioresistance and epithelial-mesenchymal transition (EMT) in EC. Firstly, a radioresistant cell line KYSE-150R was established, with an interesting discovery was observed that miR-1275 was down-regulated in KYSE-150R cells compared to the parental cells. Functionally, miR-1275 inhibition elevated radioresistance in KYSE-150 cells via promoting EMT, whereas enforced expression of miR-1275 increased radiosensitivity in KYSE-150R cells by inhibiting EMT. Mechanically, we demonstrated that miR-1275 directly targeted WNT1 and therefore inactivated Wnt/β-catenin signalling pathway in EC cells. Furthermore, WNT1 depletion countervailed the promoting effect of miR-1275 suppression on KYSE-150 cell radioresistance through hampering EMT, whereas WNT1 overexpression rescued miR-1275 up-regulation-impaired EMT to reduce the sensitivity of KYSE-150R cells to radiation. Collectively, our findings suggested that miR-1275 suppressed EMT to encourage radiosensitivity in EC cells via targeting WNT1-activated Wnt/β-catenin signalling, providing a new therapeutic outlet for overcoming radioresistance of patients with EC.
Keywords: Wnt/β-catenin; epithelial-mesenchymal transition; miR-1275; oesophageal cancer; radioresistance.
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.