scholarly journals ANGPTL3 Overexpression Suppresses the Development of Oncogenic Properties in Renal Cell Carcinoma via the Wnt/β-Catenin Signaling Pathway and Predicts Good Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yu-jian Zhang ◽  
Lin Zhang ◽  
Fei Feng ◽  
Qi-feng Cao
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Disease Free Survival ◽  
Good Prognosis ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Vessel Growth ◽  
Reporter Assays ◽  
Proliferation And Metastasis

Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth, has been reported to exhibit an abnroaml expression in many different cancers. However, the expressing pattern and functions of ANGPTL3 renal cell carcinoma (RCC) were rarely reported. In this study, we observed that ANGPTL3 expression was distinctly downregulated in both RCC specimens from TCGA datasets and cell lines. Survival assays also revealed that patients with low ANGPTL3 expression exhibited a shorter overall survival and disease-free survival than those with high ANGPTL3 expression. Cell counting kit-8 (CCK-8) assay, Colony formation assay, and flow cytometry showed that overexpression of ANGPTL3 distinctly suppressed the proliferation of RCC cells, and promoted apoptosis. Transwell assays and Wound healing assays revealed that ANGPTL3 upregulation suppressed the migration and invasion of RCC cells. Then, we explored whether ANGPTL3 dysregulation influenced the alteration of Wnt/β-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/β-catenin signaling. Overall, our results confirmed that overexpression of ANGPTL3 was related to the malignancy and good prognosis of RCC patients, and ANGPTL3 upregulation inhibited the tumor proliferation and metastasis via the Wnt/β-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.

scholarly journals Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis

2018 ◽  
Vol 46 (6) ◽  
pp. 2517-2531 ◽  
Author(s):  
Xiaobing Liu ◽  
Dangling Zhang ◽  
Yaxing Hao ◽  
Qian Liu ◽  
Yuqi Wu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Rt Pcr ◽  
E Cadherin

Background/Aims: Cyanidin is an anthocyanin found in many foods. Although its variable antioxidant levels are well-documented, little is known about its effects on renal cell carcinoma (RCC) tumorigenesis. This study, therefore, investigated the effects of cyanidin on the proliferation, migration, and invasion of renal cell carcinoma lines and demonstrated, for the first time, significant inhibitory effects of cyanidin on RCC tumorigenesis. Methods: RCC cells were treated with different doses of cyanidin and the effects were tested by Cell Counting Kit-8 reagent, clone formation assay, transwell assay, and flow cytometry. Moreover, the cyanidin-mediated mechanism that curtailed tumorigenesis was analyzed by RNA sequencing (RNA-seq). Sequencing data from The Cancer Genome Atlas (TCGA) were used to compare the expression of both early growth response protein 1 (EGR1) and selenoprotein W (SEPW1) in RCC and tumor-free adjacent normal tissue samples. Real-time PCR (RT-PCR) and/or western blot were used to assess the expression of E-cadherin, cleaved-caspase3, Bcl2, p62, and ATG4. Results: We found significantly greater induction of cell-cycle arrest, apoptosis, and suppression of RCC cell invasion and migration at concentrations of 25 µM and 100 µM than at a concentration of 50 µM. It was also discovered, first through RNA-seq then confirmed by RT-PCR, that cyanidin (100 µM) inhibited RCC carcinogenesis through EGR1 and SEPW1. TCGA data indicated that the expression level of EGR1 was lower and that of SEPW1 was higher in RCC tumor tissue than in normal tissues. Moreover, western blot and/or RT-PCR indicated that cleaved-caspase3 was enhanced and E-cadherin was inhibited by cyanidin treatment. Furthermore, western blot and RT-PCR also showed regulation of p62 and ATG4, which are associated with autophagy. Cyanidin in vivo significantly inhibited the growth of xenografts in nude mice. Conclusions: The results of this study showed the therapeutic potential of cyanidin for the treatment of RCC and the prevention of recurrence and metastasis.

scholarly journals MiR-125b promotes migration and invasion by targeting vitamin D receptor in renal cell carcinoma

2020 ◽  
Author(s):  
XiYuan He ◽  
ShangFan Liao ◽  
DongMing Lu ◽  
FaBiao Zhang ◽  
yongyang wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Vitamin D ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Proliferation And Metastasis ◽  
And Behavior

Abstract Background To investigate the expression of miR-125b and vitamin D receptor (VDR) in renal cell carcinoma (RCC) and assess the possible association between them. Then, to elucidate whether miR-125b can regulate the expression of VDR and affect proliferation and metastasis in RCC. Methods The expression of miR-125b was detected by quantitative real-time polymerase chain reaction (RT-PCR) in RCC cell lines. MiR-125b mimic and inhibitor were employed to measure the function and behavior of miR-125b in RCC cell lines. The relationship between miR-125 and VDR was verified using luciferase assays, and their expression was also examined in primary tumor and normal peritumoral kidney tissues in 20 clear cell RCC (ccRCC) samples. Results Overexpression of miR-125b promoted migration and invasion and reduced cell apoptosis in ACHN cells, while inhibition of miR-125b suppressed migration and invasion and induced cell apoptosis in 786-O cells. Overexpression of miR-125b decreased VDR expression via targeting VDR. Expression of miR-125b mRNA was significantly higher in ccRCC tissues than in normal adjacent tissues, and the expression of miR-125b mRNA negatively correlated with that of VDR (r=-0.444, p=0.04). Conclusion Overexpression of miR-125b decreased the expression of VDR and the promoted migration and invasion of RCC cells; in addition, there was a negative correlation between miR-125b and VDR expression in ccRCC.

scholarly journals miR-198 inhibits the progression of renal cell carcinoma by targeting BIRC5

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Yuan ◽  
Zhenhong Su ◽  
Shengjie Liao ◽  
Duanzhuo Li ◽  
Zhiwen Zhou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Nude Mouse ◽  
Renal Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Nude Mouse Model

Abstract Background miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC. Methods Immunohistochemistry was performed to estimate the level of survivin in RCC sections. Quantitative real-time polymerase chain reaction was performed to determine the expression level of miR-198 in fresh RCC tissues. Furthermore, the target relationship between miR-198 and BIRC5 was predicted using the TargetScanHuman 7.2 database and verified via dual-luciferase reporter assay and western blotting. The effects of miR-198 on the viability, apoptosis, invasion, and migration of A498 and ACHN cells were studied using Cell Counting Kit-8, flow cytometry, transwell migration assay, and wound healing assay, respectively. Additionally, a xenograft nude mouse model was established to evaluate the effect of miR-198 on RCC tumorigenesis. Results The expression levels of BIRC5 and miR-198 were respectively higher and lower in RCC tissues than those in normal adjacent tissues. Furthermore, miR-198 could inhibit luciferase activity and reduce the protein level of survivin without affecting the BIRC5 mRNA levels. miR-198 inhibited cell viability, migration, and invasion and promoted cell apoptosis; co-transfection with BIRC5 could rescue these effects. Moreover, miR-198 could repress tumor growth in the xenograft nude mouse model of RCC. Conclusions Our study demonstrates that miR-198 suppresses RCC progression by targeting BIRC5.

scholarly journals PYCR1 is associated with papillary renal cell carcinoma progression

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 586-592 ◽  
Author(s):  
Qiu-Li Wang ◽  
Ling Liu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Expression Profiles ◽  
Survival Rates ◽  
Papillary Renal Cell Carcinoma ◽  
Mtor Pathway ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Phosphorylated Akt

AbstractObjectiveWe aimed to determine the function of pyrroline-5-carboxylate reductase 1 (PYCR1) on progression of papillary renal cell carcinoma (PRCC) and related mechanism.MethodsThe TCGA database provided us expression profiles of PYCR1 and overall survival rates. Small interfering RNA (siRNA) was used to knockdown PYCR1; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were conducted to identify the expression levels of mRNA and protein. The cell counting kit-8 (CCK-8) and colony formation assays were used to explore cell viability in Ketr-3 cells. The migration and invasion of Ketr-3 cells were investigated by transwell assays.ResultsWe found that PYCR1 was over-expressed in PRCC tissues and cells, causing poor outcomes. Moreover, reduction of PYCR1 played a negative role on cell proliferation, migration and invasion in tumor cells. The important Akt/mTOR pathway proteins, phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR), also showed lower levels compared with control groups.ConclusionThese findings showed that disordered expression of PYCR1 could modulate PRCC progression through the Akt/mTOR pathway, implying a theoretical basis for PYCR1 as a potential therapeutic target in future clinical PRCC treatment.

scholarly journals Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 948 ◽  
Author(s):  
Hsieh ◽  
Tsai ◽  
Yang ◽  
Chiou ◽  
Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Proliferation And Metastasis

Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3‐(4,5‐cimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

scholarly journals circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis

2021 ◽  
Vol 16 (1) ◽  
pp. 362-374
Author(s):  
Xiangli Lei ◽  
Meiling Yang ◽  
Zhifang Xiao ◽  
Heng Zhang ◽  
Shuai Tan
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Growth ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Renal cell carcinoma (RCC) is a common urological malignancy. Circular RNAs (circRNAs) have been confirmed to play an important regulatory role in various cancers. This study aimed to investigate the role and potential mechanism of circTLK1 (hsa_circ_0004442) in RCC. The levels of circTLK1, Cbl proto-oncogene (CBL), and microRNA-495-3p (miR-495-3p) were detected by quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation, cycle arrest and apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, scratch, and transwell assays. The levels of E-cadherin and Vimentin were measured by western blot. The targeting relationship between miR-495-3p and miR-495-3p or CBL was verified by dual-luciferase reporter assay. Tumor growth in vivo was evaluated by xenograft assay. The results found that circTLK1 and CBL were up-regulated in RCC tissues and cells. Silencing of circTLK1 or CBL inhibited proliferation and metastasis and accelerated apoptosis in RCC cells. In addition, circTLK1 directly bound to miR-495-3p, and CBL was the target of miR-495-3p. circTLK1 sponged miR-495-3p to increase CBL expression. Moreover, knockdown of circTLK1 suppressed tumor growth in vivo. In conclusion, down-regulation of circTLK1 restrained proliferation and metastasis and promoted apoptosis in RCC cells by modulating miR-495-3p/CBL axis.

CircTLK1 Promotes the Proliferation and Metastasis of Renal Cell Carcinoma by Sponging miR-136-5p

2019 ◽  
Author(s):  
Jianfa Li ◽  
ChenChen Huang ◽  
Jing Ye ◽  
Yaoting Gui
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proliferation And Metastasis

scholarly journals Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Quan ◽  
Yuchen Bai ◽  
Yunbei Yang ◽  
Er Lei Han ◽  
Hong Bai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Disease Free Survival ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Cell Renal Cell Carcinoma ◽  
Upregulated Genes

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

Adjuvant Therapy in Renal Cell Carcinoma: Current Stance and Future Directions

Kidney Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Austin G. Kazarian ◽  
Neal S. Chawla ◽  
Ramya Muddasani ◽  
Sumanta K. Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Adjuvant Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Adjuvant Setting ◽  
Metastatic Setting

In recent years, incredible progress has been made in the treatment of metastatic renal cell carcinoma, with a paradigm shift from the use of cytokines to tyrosine kinase inhibitors, and more recently, immune checkpoint inhibitors (ICIs). Despite advances in the metastatic setting, effective therapies in the adjuvant setting are a largely unmet need. Currently, sunitinib (Sutent, Pfizer) is the only therapy for the adjuvant treatment of RCC included in the National Comprehensive Cancer Network guidelines, which was approved by the FDA based on the improvement in disease-free survival (DFS) seen in the S-TRAC trial. However, improvement in DFS has not translated into an overall survival (OS) benefit for patients at high-risk of relapse post-nephrectomy, illustrating the need for more effective therapies. This manuscript will highlight attributes of both historical and current drug trials and their implications on the landscape of adjuvant therapy. Additionally, we will outline strategies for selecting patients in whom treatment would be most beneficial, as optimal patient selection is a crucial step towards improving outcomes in the adjuvant setting. This is especially critical, given the financial cost and pharmacological toxicity of therapeutic agents. Furthermore, we will review the design of clinical trials including the value of utilizing OS as an endpoint over DFS. Finally, we will discuss how the incorporation of genomic data into predictive models, the use of more sensitive imaging modalities for more accurate staging, and more extensive surgical intervention involving lymph node dissection, may impact outcomes.

scholarly journals Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Ming-xiao Zhang ◽  
Li-zhen Zhang ◽  
Liang-min Fu ◽  
Hao-hua Yao ◽  
Lei Tan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Positive Feedback ◽  
Renal Cell ◽  
Clear Cell ◽  
Biological Significance ◽  
Specific Inhibitor ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma

AbstractLong noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

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