RESUMO
BACKGROUND: Overexpression of certain long non-coding RNAs (lncRNAs) promotes the progression of castration-resistant prostate cancer (CRPC). The significance and potential role of the lncRNA designated pituitary tumour-transforming 3, pseudogene (PTTG3P) in CRPC is unknown. METHODS: We detected PTTG3P expression by qPCR. Upregulated PTTG3P expression was performed to explore the role of PTTG3P in PCa cells resistant to ADT (androgen deprivation therapy). The relationship among PTTG3P, mir-146a-3p and PTTG1 were validated by qPCR, western blot and luciferase assay. RESULTS: PTTG3P levels were significantly increased in the androgen-independent PC cell lines, as well as in CRPC tissues compared with those of the androgen-dependent prostate cancer cell line LNCaP and tumour tissues of patients with hormone-naive prostate cancers. Enforced expression of PTTG3P in androgen-deprived LNCaP cells significantly enhanced survival, clonogenicity, and tumorigenicity. Further, PTTG3P acted as a competing endogenous RNA (ceRNA, natural miRNA sponge) to upregulate PTTG1 expression by competing for mir-146a-3p in the progression to CRPC. CONCLUSION: Our findings suggest that PTTG3P promotes the resistance of prostate cancer cells to androgen-deprivation therapy via upregulating PTTG1. PTTG3P may therefore represent a potential target for therapy of CRPC.
Assuntos
Adenocarcinoma/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Securina/biossíntese , Securina/genética , Adenocarcinoma/genética , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Animais , Antineoplásicos Hormonais/uso terapêutico , Ligação Competitiva , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Xenoenxertos , Humanos , Masculino , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Transplante de Neoplasias , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/genética , Pseudogenes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Compostos de Tosil/uso terapêutico , Ensaio Tumoral de Célula-Tronco , Regulação para CimaRESUMO
To evaluate the value of procalcitonin (PCT) as an early marker for diagnosis and differentiation of without urosepsis, urosepsis, severe urosepsis, and uroseptic shock following PCNL and the ability of PCT to assess the effectiveness of antibiotic therapy in patients with urosepsis. From June 2012 to August 2013, 267 patients undergoing PCNL for renal calculi, and who fulfilled selection criteria, were recruited into our study. The patients' medical records were reviewed retrospectively. One of selection criteria was the scores of PCT and WBC were collected at operative day, postoperative day one, day two, day three, day five and day seven. The area under the ROC curve for the prediction of urosepsis was 0.960 for PCT and 0.634 for WBC. PCT concentrations were higher in patients with uroseptic shock versus severe urosepsis versus urosepsis versus without urosepsis following PCNL. WBC values showed no significant difference between patients with urosepsis, severe urosepsis and uroseptic shock following PCNL. With time, in patients with successfully treated urosepsis following PCNL, the PCT concentrations significantly declined and kept decreasing from postoperative day two to postoperative day seven and the WBC scores showed no significant change over the first postoperative 2 days and were decreased only after postoperative day three. PCT appears to be a useful early marker to diagnosis and discriminate urosepsis, severe urosepsis and uroseptic shock following PCNL. Daily PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in urosepsis following PCNL.
