The Role Of RNA-binding Protein QKI In Prostate Cancer Progression

Prostate cancer is the most common solid tumor in man in western countries.In recent years,with the changes of age structure and dietary habits in China,the incidence of prostate cancer has been increasing year by year.But the treatment of prostate cancer still faces huge challenges.To date,the first-line treatment for advanced and metastatic prostate cancer is androgen deprivation therapy(ADT).ADT showed excellent therapeutic effects at the early stage.Most patients developed Castration resistant prostate cancer(CRPC)within 2 to 3 years.Current first-line drugs for CRPC patients are Docetaxel,Enzalutamide and Abiraterone.With the wide application of ADT,the incidence of Neuroendocrine prostate cancer(NEPC)is increasing.NEPC is a Subtype of prostate cancer.Most NEPC tumors do not express AR or PSA,but neuroendocrine markers(synaptophysin,chromogranin,CD56).NEPC does not rely on AR signaling pathway,and is resistant to ADT.Up till now,the pathogenesis of NEPC is still unclear,and there is no effective treatment for NEPC.At present,the treatment of both CRPC and NEPC is facing severe challenges,and further studies on the mechanism of the occurrence and development of prostate cancer are required.Quaking(QKI)is an RNA-binding protein,which plays an important role in regulating multiple aspects of RNA metabolism.QKI is involved in Epithelial cells-(Epithelial-Mesenchymal Transition,EMT),cell cycle,apoptosis and cell differentiation,EMT plays an important role for cancer cells to obtain migration and invasion ability,so we speculated that QKI can promote the invasion of cancer.To verify the role of QKI in the development of prostate cancer,we first analyzed the changes of QKI m RNA in patients with prostate cancer at different stages.The results showed that the expression of QKI was significantly increased in patients with metastasis,and the expressions of qki-001 and qki-006 subtypes were higher.Subsequently,Kaplan-Meier survival analysis was used to detect the relationship between QKI expression and the prognosis of prostate cancer patients.The results showed that the prostate cancer specific mortality(PCSM)and the median survival period of the invasion in the group with high QKI expression level were shorter than that in the group with low QKI expression level.It is suggested that QKI can promote the development of prostate cancer.We used cell proliferation assay to detect the effect of QKI on cell growth,and the results showed that QKI had different effects on cell proliferation in different cells.This effect may be related to cellular contents.Then we tested the effect of QKI on the ability of cell migration and invasion,and the results showed that QKI-001 and QKI-006 promoted the migration and invasion of prostate cancer cells.We tested the regulatory relationship between QKI and AR,and the results showed that there was no mutual regulatory relationship between QKI and AR.The above results suggest that QKI may play a role in promoting the metastasis of prostate cancer,and the specific mechanism still needs to be further studied.