BackgroundThe aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells.MethodsAQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay.ResultsThe results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P = 0.042), and lymph node metastasis (P = 0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P > 0.05). A positive correlation between the number of CTCs and AQP5 expression (P < 0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA.ConclusionsWe concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.

Abstract. The function of kinesin family member 18A (KIF18A) in human renal cell carcinoma (RCC) is unclear.The purpose of the current study was to determine the expression and prognostic significance of KIF18A in RCC. Specimens from 273 RCC patients undergoing nephrectomies were studied. Expression of KIF18A mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR) or quantitative PCR, and the expression of KIF18A protein was examined by immunohistochemistry and western blotting. The expression of KIF18A in clear-cell RCC cell lines was decreased using small interfering RNA targeting KIF18A, and increased by transfection with KIF18A cDNA. The proliferative ability of RCC cells in vitro and in vivo was detected by WST-1 assay and an animal xenograft model with BALB/c nude mice, respectively. The association between KIF18A expression and overall survival was calculated using Kaplan-Meier analysis. The results showed that KIF18A expression was significantly increased in RCC tissues compared with normal kidney tissues. The level of KIF18A expression was significantly associated with tumor stage, histological grade, metastasis and tumor size. Moreover, KIF18A increased the proliferation of RCC cells in vitro and in vivo. KIF18A expression was upregulated in RCC and enhanced the proliferation of RCC cells. Therefore, it appears that KIF18A plays a key role in the carcinogenesis and progression of RCC, and is a novel candidate prognostic marker for RCC patients. Furthermore, silencing KIF18A expression may serve as a new therapeutic strategy against RCC.

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein are two of the most prevalent endocrine-disrupting chemicals (EDCs) that present in the environment and food. However, how these two EDCs would affect prepubertal Sertoli cells development was rarely studied. In this study, primary prepubertal Sertoli cells were isolated from 22-day-old Sprague Dawley rats and exposed to MEHP at 1 μmol/L, 10 μmol/L, and 100 μmol/L (M1, M10, and M100), genistein at 10 μmol/L (G), and their combination (G + M1, G + M10, and G + M100). Cell proliferation inhibition rate, apoptosis and necrosis rate, and cellular redox state were evaluated. Our results revealed that MEHP could significantly increase cell proliferation inhibition rate, apoptosis rate, necrosis rate, and intracellular reactive oxidative species level. However, coadministration of genistein could partially alleviate MEHP-induced prepubertal Sertoli cells oxidative injuries via enhancement of testicular antioxidative enzymes activities and upregulation of Nrf2 and HO-1, indicating that genistein could partially attenuate MEHP-induced prepubertal Sertoli cells damage through antioxidative action and may have promising future on its curative role for attenuating other EDCs-induced reproductive disorders.

Abstract. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. TPX2 is considered to be an important gene in tumorigenesis; however, the particular function of TPX2 in the development of human renal cell carcinoma (RCC) is unknown. In the present study, the expression, function and prognostic significance of TPX2 in human RCC was analyzed. A total of 286 tissue samples from patients with RCC who had undergone nephrectomies were utilized. Subsequently, the expression of TPX2 protein was investigated using immunohistochemistry and western blotting, and TPX2 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. To establish the effect of TPX2 on the proliferation and invasion of the RCC cells, TPX2 expression was increased by stable transfection with a TPX2 vector and TPX2 expression was decreased using small interfering RNA. Proliferation of the RCC cells was analyzed using a WST-1 assay and an animal xenograft model with BALB/c nude mice, whilst invasion of the RCC cells was examined using a Matrigel-coated invasion chamber. It was demonstrated that TPX2 expression was significantly higher in the RCC tissues compared with normal kidney tissues (P<0.05). Furthermore, TPX2 expression was associated with tumor size, histological grade and tumor stage (P<0.05), and was observed to markedly increase the proliferation and invasion of the RCC cells. It may be concluded that the expression of TPX2 is significantly upregulated in RCC tissue, subsequently increasing the proliferative and invasive ability of RCC cells. Therefore, the protein may serve as a therapeutic target and independent prognostic factor in the treatment of human RCC.

Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.