kiss1-protein--human and Kidney-Neoplasms

Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression.. RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays.. We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1.. In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.

Topics: Apoptosis; Carcinoma, Renal Cell; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Female; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Kisspeptins; Male; Middle Aged; Phosphatidylinositol 3-Kinases; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Long Noncoding; RNA, Small Interfering; Signal Transduction; TOR Serine-Threonine Kinases

To evaluate Kisspeptin-10 (Kiss-10) in patients with small renal tumours (SRTs) and controls.. Kiss-10 was measured in preoperative plasma samples in a cohort of 143 patients with unilateral renal tumours smaller than or equal to 4 cm and 40 age-matched controls by a competitive ELISA test kit. The cohort of patients included 56 patients with clear cell renal cell carcinoma (ccRCC), 43 with papillary RCC (pRCC), 12 with chromophobe RCC (chRCC) and 32 with oncocytomas.. Kiss-10 was detected in all patients and controls. SRT patients revealed significantly higher Kiss-10 levels than controls (mean value 10.04 vs. 6.37 pmol/l, p < 0.001). In SRT patients, Kiss-10 was detected at significantly different concentrations between the subgroups (p = 0.021). The highest concentration was observed in those with oncocytomas (11.50 pmol/) followed by chRCC, pRCC and ccRCC patients (9.89, 10.01 and 9.25 pmol/l, respectively). Receiver operating characteristic curve analyses revealed an area under the curve (AUC) of 0.82 for the comparison of all tumours vs. controls (p < 0.001) and an AUC of 0.671 for all malignant tumours vs. oncoytomas (p = 0.003).. This study shows that Kiss-10 levels are significantly altered by malignancy and tumour subtypes even in patients with SRTs. Kiss-10 therefore deserves further attention as a plasmatic biomarker for renal tumours.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers, Tumor; Carcinoma, Renal Cell; Case-Control Studies; Cohort Studies; Female; Humans; Kidney Neoplasms; Kisspeptins; Male; Middle Aged; Prognosis; ROC Curve; Sensitivity and Specificity

Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis.

Topics: Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Kisspeptins; Lignans; Neoplasm Invasiveness; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Signal Transduction

To investigate whether the microRNA-21 gene (miR-21) could regulate renal cancer cells invasion by downregulation of TFC21 and KISS1.. Quantitative real-time polymerase chain reaction was applied to evaluate the expression level of miRNA-21 in renal cancer and normal renal cell samples. The regulated effects of miR-21 to TCF21 were detected by Western blot after pre/anti-miR-21 was transfected to Caki-1 cells. The luciferase activity assay was used to reveal the predicted target gene of miR-21 was direct and specific. Small interfering RNA-TCF21 was transfected to Caki-1 cells to inhibit the expression of the TCF21 gene. Next, the expression of the KISS1 gene was detected by Western blot in Caki-1 cells with TCF21 gene silencing. The expression vector, pcDNA3.1-KISS1, was transfected to Caki-1 cells to upregulate the expression of the KISS1 gene. The invasion ability of Caki-1 cells with KISS1 overexpression was analyzed using the Transwell assay.. Our study showed that miR-21 was upregulated in human renal cell carcinoma specimens compared with its expression in normal renal cell specimens. Pre-miR-21 could upregulate the expression of miR-21 and downregulate the expression of TCF21, and anti-miR-21 showed the opposite effects. siRNA-TCF21 decreased the expression of the TCF21 protein, and the expression of KISS1 was downregulated in Caki-1 cells with TCF21 gene silencing. pcDNA3.1-KISS1 transfection upregulated the expression of the KISS1 protein, and the invasion ability of Caki-1 cells with KISS1 overexpression decreased markedly.. Aberrantly expressed miR-21 might regulate the TCF21-KISS1-associated renal cell carcinoma cell invasion pathway, and this miRNA signature could offer a novel potential therapeutic strategy for renal cell carcinoma.

Topics: Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Renal Cell; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Kidney Neoplasms; Kisspeptins; MicroRNAs; Neoplasm Invasiveness; Transfection; Tumor Cells, Cultured; Up-Regulation

The mortality of patients with conventional renal cell carcinomas (RCC) correlates directly with the development of metastasis, which cannot be reliably predicted simply by TNM classification. The aim of this study was to identify genes associated with the tumour progression. We have analysed the global gene expression in conventional RCCs, including those with and without progression by Affymetrix GeneChip and selected the genes by gene set enrichment analysis. The expression and function of KISS1R was validated by RT-PCR, western blotting and immunohistochemistry and by in vitro experiments. An immunohistochemical and clinical follow-up study showed that lack of KISS1R expression is associated with rapid progression of tumours. In vitro studies showed that activation of KISS1/KISS1R signalling by kisspeptin treatment decreases the motility and invasive capacity of tumour cells. The kisspeptin treatment also induces the expression of KISS1R in tumour cells in vitro and activates signalling in cases without constitutional expression of the receptor. Expression of the KISS1R protein can be used for estimating the prognosis of conventional RCCs. Confirming the activation of KISS1R signalling in vivo may open a way for kisspeptin treatment of patients with conventional RCCs.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Disease Progression; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kidney; Kidney Neoplasms; Kisspeptins; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Prognosis; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Survival Analysis; Tumor Cells, Cultured; Tumor Suppressor Proteins

Topics: Carcinoma, Renal Cell; Cell Movement; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Kisspeptins; Neoplasm Invasiveness; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Tumor Suppressor Proteins

Topics: Carcinoma, Renal Cell; Cell Movement; Humans; Kidney; Kidney Neoplasms; Kisspeptins; Neoplasm Invasiveness; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Tumor Suppressor Proteins

Metastin, the final peptide of the KiSS-1 gene, has been proposed to suppress cell motility.. This study investigated whether renal cell carcinoma (RCC) tissue expresses metastin or its receptor, and clarified whether metastin can suppress migration and/or invasion and/or proliferation of RCC cells in vitro.. Twenty-five RCC samples were submitted. Fresh RCC tissues were prepared for real-time RT-PCR, and formalin-fixed and paraffin-embedded tissues blocks were examined by immunohistochemistry. RCC cell lines Caki-1 and ACHN were supplied for cell migration, invasion, and proliferation assays.. Real-time RT-PCR was performed by using Taq Man gene expression system. ENVISION system was used in immunohistochemistry. Wound-healing assay and matrigel assays were used to identify migration and invasion abilities of RCC cell lines. Cell Counting Kit-8 was applied to measure the cell proliferation. Cell morphology was examined under a META system. Statistical analysis was performed with SPSS15.0J.. In twenty-five RCC samples, the mRNA level of metastin receptor was identified to be significantly higher than non-neoplastic renal cortex by real-time RT-PCR (p=0.011). Immunohistochemical study also detected metastin receptor protein in all RCC tumors. In vitro, this study showed that metastin inhibited migration and invasion of Caki-1 and ACHN cells. In contrast, it had no effects on cell proliferation. Metastin (10 micromol/l) induced excessive formation of focal adhesions and stress fibers in Caki-1 and ACHN cells; this phenomenon was inhibited by pretreating pharmacological Rho-kinase inhibitor (Y-27632) to those cells.. This is the first report regarding overexpression of the metastin receptor hOT7T175 in human RCC. We demonstrate that metastin can inhibit migration and invasion of the RCC cell line, which is regulated by a Rho-kinase inhibitor. Metastin and its receptor are therefore probable targets for suppressing RCC.

Topics: Carcinoma, Renal Cell; Cell Adhesion; Cell Division; Cell Line, Tumor; Cell Movement; DNA Primers; Female; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Kidney Neoplasms; Kisspeptins; Male; Neoplasm Invasiveness; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Suppressor Proteins