Objective  To investigate the effect of long non-coding RNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) on the chemosensitivityof a human lung cancer cisplatin (DDP)-resistant cell line (A549/DDP) to DDP and to explore the potential underlying molecular mechanisms.

  Methods  We used quantitative real-time PCR to detect the expression of FTH1P3 and miR-218 in the A549 and A549/DDP cells. We performed MTT assay, flow cytometry analysis, Hoechst 33258 staining, and Caspase-3 activity assay to evaluate the DDP chemosensitivity of the A549/DDP cells. We analyzed the regulatory effect of FTH1P3 on miR-218 via luciferase reporter gene and RNA immunoprecipitation assays.

  Results  Compared with the A549 cells, the FTH1P3 and miR-218 expressions were up- and downregulated (P<0.05) in the A549/DDP cells, respectively. Compared with the si-NC, si-FTH1P3 increased the DDP chemosensitivity of the A549/DDP cells, showing reduced half-maximal inhibitory concentration (IC50), downregulated multidrug resistance-associated protein 1 (MRP1) and ATP-binding cassette subfamilyB member 1 (ABCB1) mRNA expressions, reduced cell growth ability, and increased apoptosis and CASP3 activity (P<0.05). Moreover, FTH1P3 directly bound to miR-218 and inhibited its expression (P<0.05). Compared with NC-inhibitors, miR-218 inhibitors reversed the DDP chemosensitivity of si-FTH1P3-treated A549/DDP cells (P<0.05).

  Conclusions  FTH1P3 expression was upregulated in A549/DDP cells, reducing the DDP chemosensitivity of A549/DDP cells through miR-218 expression downregulation-related effect or mechanism.