Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.

Purpose: We previously reported that importin 13 (IPO13), a member of the importin-beta family of nuclear import proteins, regulates nuclear import of the glucocorticoid receptor in airway epithelial cells, IPO13 serves as a potential marker for corneal epithelial progenitor cells, and IPO13 is associated with corneal cell proliferation. Here we investigated the role of IPO13 in the pathogenesis of pterygium and the underlying mechanism including interaction with other cell proliferation-related factors: keratin 17 (K17), a lesional protein and a member of the type I keratins, and c-Jun, a protein of the activator protein-1 complex.Methods: Tissue samples were collected from primary pterygia, recurrent pterygia, and normal conjunctiva to perform the following experiments: immunohistochemical measurement of IPO13 and K17. Pterygium epithelial cells (PECs) were cultured in keratinocyte serum-free defined medium to examine the expression of IPO13 and K17. Lentivirus-mediated silencing and overexpression IPO13 testing was conducted, and K17 alternation was evaluated with western blot and immunostaining. In addition, the translocation of c-Jun (a K17 regulator) was further examined after IPO13 was silenced.Results: IPO13 activity was significantly increased in the basal layer of the epithelium of the pterygium. In cultured PECs, overexpression or knockdown of the IPO13 gene increased or decreased PEC proliferation, respectively. IPO13 was colocalized with K17 in the epithelium of the pterygium, and overexpression or knockdown of the IPO13 gene induced upregulation or downregulation of K17 expression in PECs, respectively. In addition, silencing of the IPO13 gene blocked nuclear translocation of c-Jun.Conclusions: We provided novel evidence that IPO13 may contribute to the pathogenesis of pterygium via modulation of K17 and c-Jun.