scholarly journals Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using Biopsy Samples

2017 ◽  
Vol 3 (6) ◽  
pp. 590-598 ◽  
Author(s):  
Yiyu Dong ◽  
Brandon J. Manley ◽  
Maria F. Becerra ◽  
Almedina Redzematovic ◽  
Jozefina Casuscelli ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Response ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Xenografts

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

scholarly journals Various forms of HIF ‐1α protein characterize the clear cell renal cell carcinoma cell lines

IUBMB Life ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 1220-1232
Author(s):  
Monika Swiatek ◽  
Iga Jancewicz ◽  
Jakkapong Kluebsoongnoen ◽  
Renata Zub ◽  
Anna Maassen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Carcinoma Cell ◽  
Cell Renal Cell Carcinoma ◽  
Renal Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

scholarly journals Acyl-CoA Thioesterase 8 and 11 as Novel Biomarkers for Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Chao-Liang Xu ◽  
Lei Chen ◽  
Deng Li ◽  
Fei-Teng Chen ◽  
Ming-Lei Sha ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Correlation Analysis ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Functional Enrichment ◽  
Clinical Samples ◽  
Cell Renal Cell Carcinoma ◽  
Ccrcc Cell

BackgroundClear cell renal cell carcinoma (ccRCC) is essentially a metabolic disorder characterized by reprogramming of several metabolic pathways. Acyl-coenzyme A thioesterases (ACOTs) are critical enzymes involved in fatty acid metabolism; however, the roles of ACOTs in ccRCC remain unclear. This study explored ACOTs expressions and their diagnostic and prognostic values in ccRCC.MethodsThree online ccRCC datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were utilized to measure the expressions of ACOTs in paired normal and tumor tissues. Receiver operating characteristic (ROC) curves were depicted to assess the diagnostic values of ACOTs in ccRCC. Quantitative real-time PCR and immunohistochemical analysis were performed to validate the ACOT11 expression in ccRCC cell lines and clinical samples. Survival curves and Cox regression analysis were used to evaluate the predictive values of ACOTs in clinical outcome of ccRCC patients. Functional enrichment analyses and correlation analysis were carried out to predict the potential roles of ACOT8 in tumorigenesis and progression of ccRCC.ResultsACOT1/2/8/11/13 were found to be significantly downregulated in ccRCC samples. In particular, ACOT11 was decreased in almost every matched normal-tumor pair, and had extremely high diagnostic value as shown by ROC curve analysis (AUC = 0.964). The expression of ACOT11 was further verified in ccRCC cell lines and clinical samples at mRNA and protein levels. Furthermore, clinical correlation analysis and survival analysis indicated that ACOT8 was correlated with disease progression and was an independent predictor of unfavorable outcome in ccRCC. Moreover, functional analyses suggested potential roles of ACOT8 in the regulation of oxidative phosphorylation (OXPHOS), and correlation analysis revealed an association between ACOT8 and ferroptosis-related genes in ccRCC.ConclusionOur study revealed that ACOT11 and ACOT8 are promising biomarkers for diagnosis and prognosis of ccRCC, respectively, and ACOT8 may affect ccRCC development and progression through the regulation of OXPHOS and ferroptosis. These findings may provide new strategies for precise diagnosis and personalized therapy of ccRCC.

scholarly journals CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972092575
Author(s):  
Jiping Sun ◽  
Aiping Yin ◽  
Wenjing Zhang ◽  
Jia Lv ◽  
Yu Liang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Cell Renal Cell Carcinoma ◽  
Ribonucleic Acids

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC.

scholarly journals LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunxiu Yang ◽  
Jingjing Pang ◽  
Jian Xu ◽  
He Pan ◽  
Yueying Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Tumor Cell Lines ◽  
Cell Renal Cell Carcinoma ◽  
Gene Target

Abstract Background Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. Methods Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay. Results Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan–Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein–protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR. Conclusion We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

scholarly journals Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 48 (3) ◽  
pp. 1075-1087 ◽  
Author(s):  
Yan Qu ◽  
Haibing Xiao ◽  
Wen Xiao ◽  
Zhiyong Xiong ◽  
Wenjun Hu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Proliferation And Metastasis

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

DUSP4 is an Oncogenic Gene for the Carcinogenesis of Clear cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Xianyou Zeng ◽  
Changyan Zhu ◽  
Xianxin Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Tissues ◽  
Oncogenic Gene

Abstract DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the oncogenesis of Clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, we explored the expression pattern of DUSP4 in CCRCC cancer tissues and CCRCC cell lines by qRT-PCR. Furthermore, we investigated the roles of DUSP4 in CCRCC using gain-of-function and loss-of-function assays. Here, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. DUSP4 overexpression promotes the proliferation, migration and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.

scholarly journals hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Zhan ◽  
Xiao Dong ◽  
Yulin Yuan ◽  
Zheng Gong ◽  
Bohan Li
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Nude Mice ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Protein Levels ◽  
Ccrcc Cell

PurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.ResultsHIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.ConclusionOur work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway.

scholarly journals Poly(ADP)-Ribosylation Inhibition: A Promising Approach for Clear Cell Renal Cell Carcinoma Therapy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4973
Author(s):  
Yaroslava Karpova ◽  
Danping Guo ◽  
Peter Makhov ◽  
Adam M. Haines ◽  
Dmitriy A. Markov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Clonogenic Potential ◽  
High Concentrations ◽  
Parp 1 ◽  
Ccrcc Cell

Poly(ADP-ribose) polymerase 1 (PARP-1) and glycohydrolase (PARG) enzymes regulate chromatin structure, transcription activation, and DNA repair by modulating poly(ADP-ribose) (pADPr) level. Interest in PARP-1 inhibitors has soared recently with the recognition of their antitumor efficacy. We have shown that the development of clear cell renal cell carcinoma (ccRCC) is associated with extreme accumulation of pADPr caused by the enhanced expression of PARP-1 and decreased PARG levels. The most severe misregulation of pADPr turnover is found in ccRCC specimens from metastatic lesions. Both, classical NAD-like and non-NAD-like PARP-1 inhibitors reduced viability and clonogenic potential of ccRCC cell lines and suppressed growth of ccRCC xenograft tumors. However, classical NAD-like PARP-1 inhibitors affected viability of normal kidney epithelial cells at high concentrations, while novel non-NAD-like PARP-1 inhibitors exhibited activity against malignant cells only. We have also utilized different approaches to reduce the pADPr level in ccRCC cells by stably overexpressing PARG and demonstrated the prominent antitumor effect of this “back-to-normal” intervention. We also generated ccRCC cell lines with stable overexpression of PARG under doxycycline induction. This genetic approach demonstrated significantly affected malignancy of ccRCC cells. Transcriptome analysis linked observed phenotype with changes in gene expression levels for lipid metabolism, interferon signaling, and angiogenesis pathways along with the changes in expression of key cancer-related genes.

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