RESUMEN
Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of differentially expressed genes under HOTAIR overexpression and in CRPC versus benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa progression. Taken together, our results provide the first evidence of lncRNA HOTAIR as a driver for NED of PCa cells.
Asunto(s)
Sistemas Neurosecretores/citología , Neoplasias de la Próstata Resistentes a la Castración/genética , ARN Largo no Codificante/genética , Proteínas Represoras/genética , Regulación hacia Arriba , Diferenciación Celular , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Proteínas Represoras/metabolismo , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: The aim of this study was to compare the perioperative outcomes between renal hilar tumors and non-hilar tumors after robotic-assisted partial nephrectomy (RAPN). METHODS: A retrospective review of consecutive patients who underwent RAPN from December 2009 to September 2015 at our institution was recruited. Perioperative outcomes including demographic characteristics, perioperative, pathological and renal function outcomes were compared between the hilar group (n = 30) and non-hilar group (n = 170). RESULTS: In characteristics, hilar group was younger (52.4 vs. 58 years, p = 0.04) and had less body mass index (23.7 vs. 25.4 kg/m2, p = 0.018). Hilar group had larger tumor size (4.8 vs. 3.7 cm, p = 0.009), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (10.7 vs. 8.5, p < 0.001) and higher RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior description and the location relative to polar lines) score (9.0 vs. 7.4, p < 0.001). Hilar tumor was associated with longer operative time (293.6 vs. 240.5 min, p = 0.001) and warm ischemia time (39.9 vs. 21.8 min, p < 0.001). But there was no statistically difference in estimated blood loss (EBL), postoperative stay and complication rate. For pathological outcomes, there was no difference of positive margin rate and pathological T stage between these groups. For renal function outcomes, hilar tumor patients had no difference of the change of creatinine and estimated glomerular filtration rate (eGFR) at postoperative 6 and 12 month as compared with non-hilar tumor patients. CONCLUSION: For renal hilar tumor, RAPN could provide acceptable results of perioperative, pathological and renal function outcome as compared with non-hilar tumor group. Thus RAPN is a safe and effective nephron-sparing surgery technique for renal hilar tumors.