scholarly journals Study on HOXBs of Clear Cell Renal Cell Carcinoma and Detection of New Molecular Target

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Guangzhen Wu ◽  
Xiaowei Li ◽  
Yuanxin Liu ◽  
Quanlin Li ◽  
Yingkun Xu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Wnt Pathway ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma ◽  
Human Protein Atlas ◽  
Tumor Protein P53

Our study examined the transcriptional and survival data of HOXBs in patients with clear cell renal cell carcinoma (ccRCC) from the ONCOMINE database, Human Protein Atlas, and STRING website. We discovered that the expression levels of HOXB3/5/6/8/9 were significantly lower in ccRCC than in normal nephritic tissues. In ccRCC, patients with a high expression of HOXB2/5/6/7/8/9 mRNA have a higher overall survival (OS) than patients with low expression. Further analysis by the GSCALite website revealed that the methylation of HOXB3/5/6/8 in ccRCC was significantly negatively correlated to gene expression, while HOXB5/9 was positively correlated to the CCT036477 drug target. As DNA abnormal methylation is one of the mechanisms of tumorigenesis, we hypothesized that HOXB5/6/8/9 are potential therapeutic targets for patients with ccRCC. We analyzed the function of enrichment data of HOXBs in patients with ccRCC from the Kyoto Encyclopedia of Genes and Genomes pathway enrichment and the PANTHER pathway. The results of the analysis show that the function of HOXBs might be associated with the Wnt pathway and that HOXB5/6/8/9 was coexpressed with multiple Wnt pathway classical genes and proteins, such as MYC, CTNNB, Cyclin D1 (CCND1), and tumor protein P53 (TP53), which further confirms that HOXBs inhibit the growth of renal carcinoma cells through the Wnt signaling pathway. In conclusion, our analysis of the family of HOXBs and their molecular mechanism may provide a theoretical basis for further research.

scholarly journals Analysis of various potential prognostic markers and survival data in clear cell renal cell carcinoma

2017 ◽  
Vol 43 (3) ◽  
pp. 440-454 ◽  
Author(s):  
Tastekin Ebru ◽  
Oz Puyan Fulya ◽  
Akdere Hakan ◽  
Yurut-Caloglu Vuslat ◽  
Sut Necdet ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Prognostic Markers ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Mammalian SIRT4 is a tumor suppressor of clear cell renal cell carcinoma by inhibiting cancer proliferation, migration and invasion

2020 ◽  
Vol 29 (4) ◽  
pp. 453-462 ◽  
Author(s):  
Changming Wang ◽  
Chiyuan Piao ◽  
Junlong Liu ◽  
Zhe Zhang ◽  
Yuyan Zhu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Level ◽  
Migration And Invasion ◽  
Advanced Tumor Stage ◽  
Cell Renal Cell Carcinoma

OBJECTIVE: Sirtuins family are defined as class III histone deacetylases (HDACs). Recently, mammalian silent information regulator two 4 (SIRT4) has been reported to be a tumor suppressor gene in multiple cancers. The objective of the present study was to explore the potential role of SIRT4 in clear cell renal cell carcinoma (ccRCC). METHODS: We estimated SIRT4 expression levels in ccRCC and its adjacent non-neoplastic tissue by Western blotting (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics data, the clinical and survival data were also collected and analyzed. In vitro study, ccRCC cell lines were transfected with SIRT4-siRNA or lentivirus to downregulate or overexpress the expression level of SIRT4. Then, the proliferation capacity of tumor cell was assessed by 5-Ethynyl-2’-deoxyuridine (EDU) assay, cell migration and invasion capacity were assessed by Transwell assays. RESULTS: Our results indicated that the expression level of SIRT4 in ccRCC was significantly lower than the corresponding normal tissues (P< 0.001). Meanwhile, bioinformatics data and the result of WB showed that low SIRT4 expression level was obviously involved with poor overall survival and advanced tumor stage in ccRCC patients. Biological experiments demonstrated that overexpression of SIRT4 significantly reduced the proliferation, migration and invasion ability of ccRCC cells. Conversely, downregulation of SIRT4 enhanced the proliferation, migration and invasion ability of ccRCC cells. CONCLUSIONS: These findings support that SIRT4 acts as a tumor suppressor in ccRCC and might be a novel biomarker and new therapeutic target for ccRCC.

scholarly journals Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Jianyi Li ◽  
Guangzhen Wu ◽  
Yingkun Xu ◽  
Jiatong Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma ◽  
Wnt Proteins

Targeted therapy for kidney cancer has achieved significant clinical results. However, because most patients who use targeted therapy will develop drug resistance, we still need to constantly explore new therapeutic targets. Although porcupine (PORCN) as a palmitoyltransferase plays a crucial role in the activation and secretion of Wnt proteins and affects the activity of the Wnt signaling pathway, little is known about the role of PORCN in clear cell renal cell carcinoma (ccRCC). We found that PORCN is highly expressed in renal cancer cell lines and patients with renal cell carcinoma with high expression of PORCN have a poor prognosis. Pathway analysis of PORCN and its related proteins showed that PORCN played a role through the Wnt signaling pathway, and there was a strong coexpression relationship between PORCN and Wnt proteins. Therefore, PORCN may be a potential and effective target for ccRCC. In the present study, we found that LGK974 could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells. We also found that LGK974 could inhibit the migration and invasion of renal cell carcinoma and reduce the expression of mesenchymal markers. After treatment with LGK974, the expression level of β-catenin, a key protein in the classical Wnt pathway, was significantly decreased, and the expression levels of the target genes cyclin D1, c-Myc, MMP9, and MMP2 in the Wnt signaling pathway were also significantly decreased, which represented a significant decrease in the activity of the Wnt signaling pathway. At the same time, the cycle of renal cancer cells was significantly blocked. In conclusion, our results indicate that LGK974 could significantly inhibit the progression of renal cancer cells in a safe concentration range, so PORCN may be a safe and effective target for patients with renal cancer.

scholarly journals SOX17 Antagonizes the WNT Signaling Pathway and is Epigenetically Inactivated in Clear-Cell Renal Cell Carcinoma

2021 ◽  
Vol Volume 14 ◽  
pp. 3383-3394
Author(s):  
Lu Wang ◽  
Zhe Wang ◽  
Yuze Zhu ◽  
Shutao Tan ◽  
Xiaonan Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma

scholarly journals Kindlin-2 promotes clear cell renal cell carcinoma progression through the Wnt signaling pathway

2017 ◽  
Vol 38 (3) ◽  
pp. 1551-1560 ◽  
Author(s):  
Muhan Li ◽  
Xuelian Pei ◽  
Guoliang Wang ◽  
Jun Zhan ◽  
Juan Du ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma

scholarly journals Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiaju Xu ◽  
Yuenan Liu ◽  
Jingchong Liu ◽  
Yi Shou ◽  
Zhiyong Xiong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Low Expression

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 4/5 of all kidney cancers. Accumulation of minor changes in the cellular homeostasis may be one cause of ccRCC. Therefore, we downloaded the RNA sequencing and survival data of the kidney renal cell carcinoma (KIRC) cohort from the Cancer Genome Atlas (TCGA) database. After the univariate and multivariate Cox regression analyses, 19 kidney-specific differentially expressed genes (DEGs) were found. Solute Carrier Family 22 Member 12 (SLC22A12) resulted in an independent prognostic predictor for both overall survival (OS) and disease-free survival (DFS). SLC22A12 expression was lower in tumoral tissue compared to normal tissue. Moreover, patients in the SLC22A12 low expression group had a higher pathological stage and worse survival than the high expression group. Additionally, qRT-PCR assay, immunoblotting test (IBT), and immunohistochemical (IHC) analyses of cancer tissues/cells and the corresponding normal controls verified that SLC22A12 is downregulated in ccRCC. Receiver operator characteristic (ROC) curves showed that the low expression level of SLC22A12 could be a good diagnostic marker for ccRCC (AUC=0.7258; p &lt;0.0001). Gene set enrichment analysis (GSEA) showed that SLC22A12 expression levels are related to metabolism, cell cycle, and tumor-related signaling pathways. GO and KEGG analyses revealed that SLC22A12 transports multiple organic compounds, ions, and hormones and participates in the extracellular structure organization. Furthermore, SLC22A12 over-expression in vitro inhibited the proliferation, migration, and invasion of renal cancer cells by regulating PI3K/Akt pathways. Such effects were reversed when knocking out SLC22A12. In summary, as a transporter for many vital metabolites, SLC22A12 may affect tumor cell survival through its impacts on the mentioned metabolites. In conclusion, this study uncovered that SLC22A12 is a promising prognostic and diagnostic biomarker for ccRCC.

scholarly journals Identification of a Novel Glycolysis-Related Gene Signature Correlates With the Prognosis and Therapeutic Responses in Patients With Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengtong Lv ◽  
Lin Qi ◽  
Xiheng Hu ◽  
Miao Mo ◽  
Huichuan Jiang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Gene Signature ◽  
Human Protein ◽  
Related Gene ◽  
Cell Renal Cell Carcinoma ◽  
Human Protein Atlas

BackgroundAccumulating evidences indicate significant alterations in the aerobic glycolysis in clear cell renal cell carcinoma (ccRCC). We aim to develop and validate a glycolysis-related genes signature for predicting the clinical outcomes of patients with ccRCC.MethodsmRNA expression profiling of ccRCC was obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. The protein expression levels of the core genes were obtained from the Human Protein Atlas database. We used four external independent data sets to verify the predictive power of the model for prognosis, tyrosine kinase inhibitor (TKI) therapy, and immunotherapy responses, respectively. Finally, we explored the potential mechanism of this signature through gene set enrichment analysis (GSEA).ResultsThrough the GSEA, glycolysis-related gene sets were significantly different between ccRCC tissues and normal tissues. Next, we identified and constructed a seven-mRNA signature (GALM, TGFA, RBCK1, CD44, HK3, KIF20A, and IDUA), which was significantly correlated with worse survival outcome and was an independent prognostic indicator for ccRCC patients. Furthermore, the expression levels of hub genes were validated based on the Human Protein Atlas databases. More importantly, the model can predict patients’ response to TKI therapy and immunotherapy. These findings were successfully validated in the external independent ccRCC cohorts. The mechanism exploration showed that the model may influence the prognosis by influencing tumor proliferation, base mismatch repair system and immune status of patients.ConclusionsOur study has built up a robust glycolysis-based molecular signature that predicts the prognosis and TKI therapy and immunotherapy responses of patients with ccRCC with high accuracy, which might provide important guidance for clinical assessment. Also, clinical investigations in large ccRCC cohorts are greatly needed to validate our findings.

scholarly journals A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Jiyue Wu ◽  
Feilong Zhang ◽  
Jiandong Zhang ◽  
Zejia Sun ◽  
Changzhen Hao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Functional Enrichment ◽  
Hippo Signaling ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

scholarly journals SPOP–PTEN–SUFU axis promotes progression of clear cell renal cell carcinoma via activating SHH and WNT pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Bo’ang Han ◽  
Zhen Sun ◽  
Tingting Yu ◽  
Yu Wang ◽  
Lun Kuang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Wnt Pathway ◽  
Clear Cell ◽  
E3 Ligase ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

AbstractAlthough E3 ligase Speckle type BTB/POZ protein (SPOP) promotes tumorigenesis by acting as a key regulatory hub in clear cell renal cell carcinoma (ccRCC), the detailed molecular mechanism remains unclear. Here, we demonstrate that a well-known tumor suppressor, Suppressor of Fused (SUFU), is downregulated by SPOP. Interestingly, this downregulation depends on cullin-3(Cul3)-SPOP E3 ligase, but SUFU is not a direct substrate of SPOP. Phosphatase and tensin homolog (PTEN), a ubiquitinated substrate of SPOP, is involved in SPOP-mediated SUFU reduction. Importantly, inhibition of SUFU leads to elevated SHH and WNT signaling, consequently rescuing the reduced proliferation, migration, and invasion abilities of ccRCC cells caused by SPOP-knockdown. Moreover, combinatorial treatment with SHH and WNT inhibitors shows more effective for suppressing ccRCC cell proliferation and aggressiveness. These findings demonstrate that a novel SPOP–PTEN–SUFU axis promotes ccRCC carcinogenesis by activating SHH and WNT pathway, providing a new treatment strategy for ccRCC.

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