The Role And Mechanism Of MicroRNA-16-5p In Radiation Response Of Prostate Cancer

Prostate cancer is the second most common cancer among men in the world.In China,the latest National Cancer Statistical Report released by the National Cancer Center clearly points out that the rising trend of male prostate cancer is fast in recent years,which has ranked the sixth in male incidence,and should be focused on in the future cancer prevention and control.Radiotherapy is the most common and effective treatment for prostate cancer because of its good curative effect,wide indications and few complications.However,about one-third of prostate cancer patients will eventually relapse after radiotherapy.Therefore,how to improve the radiotherapy effect of prostate cancer cells,and effectively kill tumor cells,is still an urgent problem for clinicians and researchers.Heavy ions are recognized as the most ideal radiotherapy rays in the 21st century,especially suitable for intractable cases that are invalid or prone to recurrence in surgery,chemotherapy,and conventional radiotherapy.Our study found that compared with the traditional X-ray irradiation,carbon ion irradiation showed significant advantages in prostate cancer cells,including more serious DNA damage,stronger inhibition of cell viability,a higher level of cell cycle arrest and apoptosis,which provides some basic data for the application of carbon ion in the clinical treatment of prostate cancer.MicroRNAs?MiRNAs?play an important role in various stages of cell ionizing radiation response through regulating the expression of various target genes.Here,we analyzed the miRNA expression profile in prostate cancer cells after carbon ion and X-ray irradiation by using miRNA probe hybridization chip technology.The results showed that the miRNA expression profiles induced by carbon ion and X-ray irradiation were different.In addition,compared with the X-ray irradiation group,irradiation of ¹²C⁶⁺ions at 70kev/?M caused more changes in miRNA expression.Furthermore,it is worth noting that compared with PC-3 cells,both X-ray irradiation and carbon ion irradiation in LNCaP cells caused more changes in miRNA expression.We screened miRNA with different expression before and after irradiation,and found that the expression of microRNA-16-5p?miR-16-5p?was up-regulated after X-ray and¹²C⁶⁺irradiation.MiR-16-5p is one of the earliest reported miRNAs associated with human malignant tumors,and we subsequently explored its role in prostate cancer.The results showed that mi R-16-5p is significantly down-regulated in prostate cancer cells,and it inhibited cell viability,regulated cell cycle distribution and induced apoptosis.AKT3 is a direct target of miR-16-5p,and miR-16-5p functions as a tumor suppressor by directly targeting AKT3.The mechanism may be through regulation PI3K/AKT/mTOR pathway.In addition,miR-16-5p plays an important role in the radiation response of prostate cancer cells.X-ray irradiation significantly induced the expression of miR-16-5p,and overexpression of mi R-16-5p can enhance the radiosensitivity of prostate cancer cells.The mechanism may be through directly targeting cyclin D1/E1 to regulate cyclin D1/E1-Rb-E2F1 signal pathway,leading to the cell cycle arrest in the G0/G1 phase,thus affecting the radiosensitivity of prostate cancer cells.Finally,the mechanism of radiation response of miR-16-5p is discussed.The results showed that X-ray irradiation induced the expression of mi R-16-5p mainly through affecting the nuclear processing stage of miR-16-5p.As a radiation response protein,p53 probably participated in the nuclear processing of miR-16-5p after irradiation,and eventually led to the increase of miR-16-5p expression.To sum up,in this study,mi RNA expression profiles in prostate cancer cells after carbon ion and X-ray irradiation were analyzed by using mi RNA probe hybridization chip technology.It was found that miR-16-5p is a radiation responsive miRNA,and its role in the development and radiation response of prostate cancer was discussed.Additionally,the mechanism of radiation response of miR-16-5p was preliminarily studied.This study provides some basic data for the application of heavy ions in the clinical treatment of prostate cancer,and miR-16-5p,as a tumor suppressor and radiosensitized miRNA in prostate cancer,may help to develop a new miRNA-based treatment stategy for prostate cancer,and overcome the radiation resistance phenomenon in the radiotherapy of prostate cancer.The study can provide a new idea for the treatment of prostate cancer.