RESUMO
Growing evidence points at an association between microRNAs and tumor development. Although dysregulation of microRNA-103a-3p (miR-103a-3p) in multiple human cancers has been reported, its expression in prostate cancer (PCa) remains unknown and there is currently no research on the relationship between miR-103a-3p and tumor protein D52 (TPD52) in PCa. Our aim in this study was to explore the effect and potential mechanism of miR-103a-3p in PCa. qRT-PCR was performed to detected the level of miR-103a-3p in PCa tissues and cells, and in normal tissues. Colony, wound-healing, invasion, proliferation, and apoptosis assays were performed in search miR-103a-3p effect in PCa. TargetScan was used to predict potential targets of miR-103a-3p. Additionally, dual-luciferase reporter, western blot, and immunofluorescence assays were performed to detected the target gene of miR-103a-3p. Finally, we explore the differences in tumor xenograft experiments between nude mice injected with stably miR-103a-3p expressing cells and those expressing a miR-negative control. Low level of miR-103a-3p was detected in PCa tissues and cells, when compared with normal tissues. Enhancement of miR-103a-3p significantly inhibited migration and invasion of PCa cells, and negatively regulated expression of the oncogenic tumor protein D52 (TPD52) through direct binding to its 3'-UTR. Interestingly, overexpression of TPD52 significantly attenuated the effect of mir-103a-3p on PCa. Our study provides the first evidence that miR-103a-3p directly targets TPD52 and inhibits the proliferation and invasion of PCa. This finding helps clarify the role of mir-103a-3p-TPD52 axis in PCa and may provide new therapeutic targets for the disease.
Assuntos
MicroRNAs , Proteínas de Neoplasias/genética , Neoplasias da Próstata , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias da Próstata/genética , Fatores de TranscriçãoRESUMO
Prostate cancer (PCa) is the second most common malignant tumors for male patients worldwide. However, whether a history of pre-existing cancer cases may affect the survival of prostate cancer patients is still not fully understood.We identified patients diagnosed with PCa between 2000 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) linked database. We further made propensity score matching and then compared all-cause and cancer-specific survival between patients with and those without a pre-existing cancer. Cox proportional hazards models and Kaplan-Meier analysis were used for survival comparison.A total of 153,255 patients with PCa were included for analysis, of whom 5939 had a history of pre-existing cancer, including hematologic and lymph (11%), intestine (19%), urinary system (36%), head and neck (9%), lung (5%), skin (12%), and others (8%). Patients with a pre-existing cancer had a worse prognosis compared with those without a pre-existing cancer [all-cause death: hazard ratio (HR)â=â2.74, Pâ<â.001; cancer-special death: HRâ=â3.98, Pâ<â.001]. Importantly, cancers in urinary bladder prior to PCa had a most adverse impact on all-cause (HRâ=â5.00, Pâ<â.001) and cancer-specific death risk (HRâ=â10.45, Pâ<â.001). Time between the pre-existing cancer and PCa had a dose-dependent effect on survival of PCa patients, with a decreased death risk as the increase of the interval time.Pre-existing cancer has a negative impact on the prognosis of patients with PCa, which is most evident in the presence of a pre-existing urinary bladder cancer. Our results provide epidemiologic evidence with low between-group bias, large sample size, and long-term follow-up, highlighting the need for site-, and interval-time-based clinical management for patients with PCa who had a pre-existing cancer.