Background
Long noncoding RNA (lncRNA)-PRLB (progression-associated lncRNA in breast cancer) has been identified to enhance the drug resistance of breast cancer cells. In this study, the authors explored PRLB effect in the paclitaxel (Tax) resistance of ovarian cancer cells and revealed the role of RSF1 (remodeling and spacing factor 1)/nuclear factor kappaB (NF-κB) signaling in this process. Materials and
Conclusion
This study reveals that knockdown of PRLB improves the sensitivity of ovarian cancer cells to Tax, at least in part, through inhibiting the activation of RSF1/NF-κB signaling through targeting miR-150-5p.
Methods
Tax resistance was established in CAOV3 and SKOV3 cell lines. The expressions of PRLB in Tax resistant tissues and cells of ovarian cancer were detected using the real time polymerase chain reaction assay. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] and flow cytometry were used to detect cell survival and apoptosis. The RNA-binding protein immunoprecipitation (RIP) assay and/or the luciferase gene reporter assay were used to assess the cross talk among miR-150-5p and PRLB/RSF1.
Results
PRLB expression was obviously enhanced in the Tax resistant ovarian cancer tissues and cells. Depletion of PRLB induced a significant decrease in the IC50 value of the CAOV3/Tax and SKOV3/Tax cells and increased cell apoptosis, as well as increased miR-150-5p expression through a direct binding. In addition, miR-150-5p upregulation decreased the luciferase activity of PRLB and RSF1, whereas this effect was abolished when the putative binding sites were mutated. And overexpression of RSF1 significantly rescued the effect of PRLB downregulation-caused decrease in the IC50 value and the increase in cell apoptosis and the decreased expressions of RSF1 and p-p65.