scholarly journals Increased expression of SET domain-containing proteins and decreased expression of Rad51 in different classes of renal cell carcinoma

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Si Liu ◽  
Yiyang Li ◽  
Hongmei Xu ◽  
Kaichen Wang ◽  
Nan Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Chromatin Immunoprecipitation ◽  
Renal Cell ◽  
Specific Binding ◽  
Set Domain ◽  
Tissue Samples

Because of scant availability of tissue samples, we did not perform elaborate examination of chromatin immunoprecipitation and specific binding of SET domain-containing proteins to the promoters of Rad51. These remain avenues for future investigations.

Protein profiling of microdomains purified from renal cell carcinoma and normal kidney tissue samples

2012 ◽  
Vol 8 (4) ◽  
pp. 1007-1016 ◽  
Author(s):  
F. Raimondo ◽  
L. Morosi ◽  
C. Chinello ◽  
R. Perego ◽  
C. Bianchi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kidney Tissue ◽  
Protein Profiling ◽  
Normal Kidney ◽  
Tissue Samples ◽  
Normal Kidney Tissue

scholarly journals LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Quan Hong ◽  
Shuqiang Wang ◽  
Shuxin Liu ◽  
Xiangmei Chen ◽  
Guangyan Cai
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kidney Tissue ◽  
The Cancer Genome Atlas ◽  
Gene Methylation ◽  
Cell Renal Cell Carcinoma ◽  
Tissue Samples ◽  
Downstream Signaling ◽  
Cancer Genome Atlas

Clear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. It is an urgent mission to find more therapeutic targets for advanced ccRCC. Leucine-rich a-2-glycoprotein 1 (LRG1) is a secreted protein associated with a variety of malignancies. Our study focused on the expression and mechanism of LRG1 in ccRCC based on data from The Cancer Genome Atlas (TCGA) and provided primary verification including LRG1 expression detection, LRG1 gene methylation detection, and downstream signaling detection. We found that LRG1 was overexpressed in ccRCC kidney tissue samples, and the methylation level of LRG1 gene was significantly decreased in ccRCC. Moreover, the expression of LRG1 was negatively related to patient survival. Based on our previous study and the verification reported in this article, we propose that demethylation-induced overexpression of LRG1 is likely to accelerate ccRCC progression via the TGF-β pathway.

scholarly journals CENPF Promotes Proliferation of Renal Cell Carcinoma In Vitro

2021 ◽  
Author(s):  
Ji Zhang ◽  
Shushu Yuan ◽  
Hua Zhu ◽  
Zhan Chen ◽  
Zhenmin Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Drug Targets ◽  
Tissue Samples ◽  
Clinical Biomarkers

Abstract Background: Metastasis and drug resistance are the main causes of renal cell carcinoma (RCC) mortality. Currently, there are still limited number of targeted therapies against advanced RCC. It is critical to develop new effective clinical biomarkers and drug targets in RCC. Several studies have shown that Centromere protein F (CENPF), a microtubule binding protein, promotes cancer progression in various types of cancer. The purpose of this study is to explore the role of CENPF in RCC.Materials and methods: Peripheral blood and corresponding tissue samples of 23 RCC patients and 23 normal physical examination patients who were treated in our hospital from 2018 to 2020 were collected, and the CENPF expression was detected by qRT-PCR, Western-blot and immunohistochemical methods. Down-regulate the expression of CENPF by siRNA transfection, and detect the proliferation of the corresponding RCC cells and the corresponding cell cycle.Results: According to TCGA data analysis, CENPF is highly expressed in RCC, and its expression level is significantly related to the overall survival and recurrence-free survival of RCC. In addition, high expression of CENPF was found in the tissues of RCC patients in our hospital. Knockdown of CENPF can significantly reduce the proliferation of RCC cells in in vitro experiments, and knockdown of CENPF can regulate the cell cycle by inhibiting the expression of cyclins such as CDK4, CDK6 and CyclinD1. Conclusion: CENPF can be used as an independent prognostic factor of RCC and regulate the proliferation ability and cell cycle of RCC cells. CENPF is a potential oncogene and prognostic marker in RCC.

scholarly journals Long noncoding RNA SNHG4 promotes renal cell carcinoma tumorigenesis and invasion by acting as ceRNA to sponge miR-204-5p and upregulate RUNX2

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Wu ◽  
Tingting Liu ◽  
Lulu Sun ◽  
Shaojin Zhang ◽  
Gang Dong
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Mouse Models ◽  
Cell Lines ◽  
Renal Cell ◽  
Cell Counting ◽  
Tissue Samples ◽  
Qrt Pcr

Abstract Background Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of human cancers, including renal cell carcinoma (RCC). Small nucleolar RNA host gene 4 (SNHG4) is reported to play an essential role in tumor growth and progression. However, the molecular mechanisms and function of SNHG4 in RCC remain undocumented. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine expression levels of SNHG4 in RCC tissue samples and cell lines. Cell counting kit-8, western blotting, activities of caspase-3, -8, and -9, wound-healing, and transwell invasion assays were performed to explore cell proliferation, apoptosis, migration, and invasion. The interaction among SNHG4, miR-204-5p, and RUNX2 was verified by bioinformatic analysis, a luciferase gene report, qRT-PCR, western blot analysis, and RNA immunoprecipitation assays. Xenograft mouse models were carried out to examine the role of SNHG4 in RCC in vivo. Results SNHG4 was highly expressed in RCC tissue samples and cell lines, and its upregulation was significantly involved in node involvement, distant metastasis, and reduced overall and relapse-free survival of patients with RCC. SNHG4 acted as an oncogenic lncRNA with promoted RCC cell proliferation, migration, invasion, and inhibited apoptosis. SNHG4 boosted tumor growth in xenograft mouse models. Mechanistically, SNHG4 functioned as a competing endogenous RNA (ceRNA) for sponging miR-204-5p, leading to the upregulation of its target RUNX2 to promote RCC cell proliferation and invasion. Conclusion SNHG4 and miR-204-5p might be indicated in RCC progression via RUNX2, suggesting the potential use of SNHG4/miR-204-5p/RUNX2 axis in RCC treatment.

Association of reduced GATA1 mRNA expression with clinicopathology and shortened recurrence-free survival in clear cell renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 521-521
Author(s):  
Inga Peters ◽  
Natalia Dubrowinskaja ◽  
Michael Kogosov ◽  
Mahmoud Abbas ◽  
Joerg Hennenlotter ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Distant Metastasis ◽  
Renal Cell ◽  
Clear Cell ◽  
Tissue Samples ◽  
P53 Expression ◽  
Expression Levels

521 Background: GATA1, a zinc-finger transcription factor and member of the GATA family proteins 1-6, is known to be involved in cell growth and apoptosis, especially in the erythroid lineage. Recent studies demonstrated that GATA1 interacts with p53 and its overexpression leads to an inhibition of the p53 gene function. Increased p53 expression levels have been shown to be associated with prognosis and tumor progression in renal cell carcinoma. Methods: Quantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA1 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA1 expression levels were determined using the ΔΔCt method. Results: The mean GATA1 expression levels were significantly decreased in tumor tissues compared to adjacent normal tissues (p < 0.001, paired t-test). In univariate logistic regression analysis decreased GATA1 mRNA expression was associated with advanced tumor disease (p = 0.005), positive status of distant metastasis (p = 0.03) and lymph node metastasis (p = 0.011). Reduced GATA1 expression was associated with an increase risk of disease recurrence (p = 0.005, hazard ratio HR = 0.05). Status of distant metastasis remained also a significant independent parameter in the bivariate Cox regression model (p = 0.05, HR = 3.01). Conclusions: GATA1 mRNA expression is reduced in ccRCC and associates with a poor clinical outcome and worse clinicopathology, indicating a possible role of GATA1 in tumor development and aggressiveness of ccRCC. GATA1 could therefore serve as a new biomarker for tumor progression in ccRCC.

scholarly journals MiR-122 promotes renal cancer cell proliferation by targeting Sprouty2

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769118 ◽  
Author(s):  
Zijie Wang ◽  
Chao Qin ◽  
Jing Zhang ◽  
Zhijian Han ◽  
Jun Tao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Carcinoma Cell ◽  
Tissue Samples ◽  
Renal Cell Carcinoma Cell ◽  
Carcinoma Tissue ◽  
Primary Renal Cell Carcinoma ◽  
Renal Cell Carcinoma Tissue

MicroRNAs are short non-coding RNAs, which have been implicated in several biological processes. Aberrant expression of the microRNA miR-122 has frequently been reported in malignant cancers. However, the mechanism underlying the effects of miR-122 in renal cell carcinoma remains unknown. The aim of this study was to determine the biological function of miR-122 in renal cell carcinoma and to identify a novel molecular target regulated by miR-122. We measured the expression levels of Sprouty2 in six renal cell carcinoma tissue samples and adjacent non-tumor tissues by western blot analysis. We then used reverse transcription polymerase chain reaction to measure miR-122 levels in 40 primary renal cell carcinoma and adjacent non-malignant tissue samples. The effects of miR-122 down-regulation or Sprouty2 knockdown were evaluated via Cell Counting Kit-8 assay, flow cytometry, and western blot analysis. The relationship between miR-122 and Sprouty2 was determined using dual-luciferase reporter assays. Sprouty2 was down-regulated in renal cell carcinoma tissue samples compared with adjacent normal tissue. In contrast, miR-122 was up-regulated in primary renal cell carcinoma tissue samples compared with adjacent normal tissue samples. Down-regulation of miR-122 substantially weakened the proliferative ability of renal cell carcinoma cell lines in vitro. In contrast, Sprouty2 knockdown promoted the in vitro proliferation of renal cell carcinoma cell lines. The spry2 gene could therefore be a direct target of miR-122. In conclusion, miR-122 could act as a tumor promoter and potentially target Sprouty2. MiR-122 promotes renal cell carcinoma cell proliferation, migration, and invasion and could be a molecular target in novel therapies for renal cell carcinoma.

scholarly journals SETD2 deficiency impairs β-catenin destruction complex to facilitate renal cell carcinoma formation

2020 ◽  
Author(s):  
Hanyu Rao ◽  
Xiaoxue Li ◽  
Min Liu ◽  
Jing Liu ◽  
Wenxin Feng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Set Domain ◽  
Cell Renal Cell Carcinoma ◽  
Incurable Disease ◽  
First Time

AbstractClear cell renal cell carcinoma (ccRCC) is a largely incurable disease that is highly relevant to epigenetic regulation including histone modification and DNA methylation. SET domain–containing 2 (SETD2) is a predominant histone methyltransferase catalyzing the trimethylation of histone H3 Lysine 36 (H3K36me3) and its mutations are highly relevant to clear cell renal cell carcinoma (ccRCC). However, its physiology role in ccRCC remains largely unexplored. Here we report that Setd2 deletion impairs the β-catenin destruction complex to facilitate ccRCC formation in a c-MYC-generated polycystic kidney disease (PKD) model, which can be relieved by an inhibitor of β-catenin-responsive transcription. Clinically, SETD2 loss is widely observed in ccRCC samples, and negatively correlated with expression of some members of β-catenin destruction complex, but positively correlated with the activation of Wnt/β-catenin signaling. Our findings thus highlight a previously unrecognized role of SETD2-mediated H3K36me3 modification in regulation of Wnt/β-catenin pathway in ccRCC.SummaryOur findings for the first time reveal a previously unrecognized role of the SETD2-mediated H3K36me3 modification in regulation of the Wnt/β-catenin pathway in ccRCC and shed light on the molecular mechanisms underlying the formation of renal cell carcinoma with epigenetic disorders.

GAPDH, YWHAZ, and RRN18S as control reference genes for gene expression studies on renal cell carcinoma (RCC) formaldehyde-fixed paraffin-embedded (FFPE) tissue samples.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 389-389
Author(s):  
V. Medina Villaamil ◽  
S. Vazquez-Estevez ◽  
B. Campos ◽  
L. Leon Mateos ◽  
J. L. Fírvida ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Stable Gene ◽  
Cell Renal Cell Carcinoma ◽  
Tissue Samples ◽  
Expression Studies ◽  
Light Cycler

389 Background: It is mandatory to have a control reference gen (RG) to correctly measure gene expression by real-time quantitative PCR (qPCR). The purpose of this study was to test a panel of 12 RGs (Human Endogenous Control Gene Panel, tataabiocenter) in order to select and validate the most appropriate control genes for expression studies on FFPE RCC tissues. Methods: qPCR followed by Normfinder and geNorm-based analysis was employed (GenEx Standard). The study was performed on 9 selected RCC tumor samples with different local stage (T1, T2 and T3). The most representative RCC histologies were also collected; clear-cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC) and cromophobe renal cell carcinoma (cRCC). A commercial pool (Biochain) of 5 cases of normal kidney was analyzed too. All samples were measured in triplicate. Expression levels of RGs: GAPDH, TUBB, PPIA, ACTB, YWHAZ, RRN18S, B2M, UBC, TBP, RPLP, GUSB and HPRT1 were measured by qPCR on a Light Cycler 480 (Roche) utilizing Light Cycler 480 SYBR Green I Master (Roche). Results: The analysis of experimental data showed that RRN18S is the most stable gene found in our FFEP RCC samples followed by GUSB and TBP. In contrast, ACTB was found to be the least stable gene between our samples. GAPDH together with YWHAZ was showed as the pair of genes introducing the least systematic error into data normalization (M-value < 1) needed to conduct expression gene studies further. Conclusions: These data suggest that GAPDH, YWHAZ and RRN18S are the most suitable RGs for gene expression profile studies in FFEP RCC. Standardization of RGs will help us to compare results from translational studies on RCC FFPE samples genes profiling. No significant financial relationships to disclose.

Correlation of germline MET mutation with response to the dual Met/VEGFR-2 inhibitor foretinib in patients with sporadic and hereditary papillary renal cell carcinoma: Results from a multicenter phase II study (MET111644).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 372-372 ◽  
Author(s):  
Ramaprasad Srinivasan ◽  
Donald P. Bottaro ◽  
Toni K. Choueiri ◽  
Ulka N. Vaishampayan ◽  
Jonathan E. Rosenberg ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Safety Data ◽  
Papillary Renal Cell Carcinoma ◽  
Chromosome 7 ◽  
Tissue Samples ◽  
Mutational Status ◽  
Pathway Activation

372 Background: Activating mutations and/or amplifications in MET have been described in patients (pts) with papillary renal cell carcinoma (PRC). Foretinib, an oral multi-kinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors, was evaluated in a phase 2 study in pts with PRC. An important objective of this study was to evaluate whether activation of the MET receptor pathway by mutation, amplification, or gain of chromosome 7 was predictive for or correlated with clinical outcomes. Methods: Pts were stratified based on status of MET pathway activation. Blood samples were collected at screening for determination of germline MET mutational status. Archival tumor tissue samples were obtained for the analysis of somatic MET mutation, amplification of the MET locus (7q31), and gain of chromosome 7 using standardized assays. Results: A total of 74 pts were enrolled on the trial (37 each in intermittent and daily dosing arms); overall efficacy and safety data are reported separately at this meeting. Sixty-seven pts were evaluable for both mutation status and response. 5/10 pts (50%) with a germline MET mutation experienced a PR, while 5 pts (50%) had SD as their best response, including 4 pts who demonstrated tumor SLD reductions of > 10%, but did not achieve PR by RECIST 1.0. Responses were also seen in pts without germline MET mutation. However, the presence of a germline MET mutation was highly predictive of a response as only 5/57 pts (9%) without a mutation experienced a PR. Other measures of MET pathway activation did not appear to correlate with activity with only 1/5 pts (20%) with somatic MET mutation having a PR; furthermore, in the absence of a concomitant MET mutation, no responses were seen in patients with MET amplification (n=2) and only 1/18 (5%) pts with a gain of chromosome 7 experienced a PR. Conclusions: The presence of germline MET mutations correlated strongly with activity of the MET inhibitor foretinib in pts with PRC. These data provide early proof of principle that MET may be a valid therapeutic target in a subset of patients with PRC.

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