Suppression of the karyopherin protein importin β1 expression inhibits prostate cancer cell proliferation

Prostate cancer (PCa) is a common malignant tumor and the second most prevalent cancer in men worldwide. Considering the prevalence, morbidity and mortality of PCa in males, understanding the molecular mechanisms that regulate PCa tumorigenesis is essential and may provide novel therapeutic strategies for PCa treatment. Importin β1 belongs to the karyopherin β family members, which is reported to play important roles in the occurrence and development of tumors. However, the expression mechanisms and physiological significance of importin β1 in PCa remains unknown. In this study, the expression of importin β1 and its involvement in PCa were studied. We found that the mRNA and protein expression levels of importin β1 were much higher in PCa cells than that in normal prostate cells. Indirect immunofluorescence assay showed that importin β1 was localized around the nuclear envelope of PCa cells compared with the nuclear localization of importin β1 in normal prostate cells. In addition, siRNA-mediated knockdown of importin β1 not only inhibited PCa cell proliferation, invasion and migration, but also promoted PCa cell apoptosis. Further study revealed that the decreased level of Mcl-1 and increased levels of Cytochrome C, Caspase-3, and the growth inhibitory proteins p53, p27, p21 and p18 might contribute to the apoptosis observed in PC-3 cells when importin β1 was inhibited. In summary, our findings suggested that importin β1 is involved in the progression of PCa and may be a potential therapeutic target for PCa treatment.