Open Access

Circular RNA FOXO3 accelerates glycolysis and improves cisplatin sensitivity in lung cancer cells via the miR‑543/Foxo3 axis

  • Authors:
    • Yanni Zhang
    • Pan Ge
    • Dangxia Zhou
    • Rong Xing
    • Lizhi Bai
  • View Affiliations

  • Published online on: October 18, 2021     https://doi.org/10.3892/ol.2021.13100
  • Article Number: 839
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑small cell lung cancer (NSCLC) is the most common cause of cancer‑associated mortality worldwide. Our previous study revealed that circular RNA (circRNA)‑FOXO3 is highly expressed in lung cancer and inhibits cell proliferation. However, to the best of our knowledge, at present, no study has focused on the specific mechanism of circRNA‑FOXO3 in drug resistance. Therefore, the present study aimed to provide novel perspectives on the role of circRNA‑FOXO3 in cisplatin (DDP) resistance in NSCLC. A Cell Counting Kit‑8 assay was used to determine the viability of cells overexpressed with circRNA‑FOXO3 and under DDP treatment. Glycolysis was analyzed by measuring glucose consumption and lactate production. The interaction of circRNA‑FOXO3, microRNA 543 (miR‑543) and Foxo3 was confirmed using a dual‑luciferase reporter assay. It was revealed that circRNA‑FOXO3 improved cell sensitivity to DDP and repressed glycolysis in DDP‑sensitive and DDP‑resistant NSCLC cells. Bioinformatics analysis, luciferase reporter assays, quantitative PCR and RNA pull‑down assays were employed to verify the binding of circRNA‑FOXO3 to miR‑543. Functionally, inhibition of miR‑543 could sensitize NSCLC cells to DDP, and overexpression of miR‑543 at least partially abolished the circRNA‑FOXO3‑induced decrease in chemoresistance. Furthermore, it was revealed that Foxo3 was a direct target of miR‑543. Notably, the inhibitory action of miR‑543 silencing on DDP resistance and glycolysis was reversed by overexpression of Foxo3 in DDP‑sensitive and DDP‑resistant NSCLC cells. In conclusion, the present study demonstrated that circRNA‑FOXO3 promoted DDP sensitivity in NSCLC cells by regulating the miR‑543/Foxo3 axis‑mediated glycolysis balance. The present findings may provide novel perspectives for the treatment of patients with NSCLC resistant to DDP.
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