scholarly journals TRIM2 downregulation in clear cell renal cell carcinoma affects cell proliferation, migration, and invasion and predicts poor patients’ survival

2018 ◽  
Vol Volume 10 ◽  
pp. 5951-5964 ◽  
Author(s):  
Wen Xiao ◽  
Xuegang Wang ◽  
Tao Wang ◽  
Jinchun Xing
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma

scholarly journals miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN

2020 ◽  
Author(s):  
Bin Gao ◽  
Lijuan Wang ◽  
Yubo Zhang ◽  
Na Zhang ◽  
Miaomiao Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Regulated Expression ◽  
Ccrcc Cell

Abstract Objective: Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods: Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Results: miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Additionally, overexpressing miR-129-5p markedly reduced SPN expression in tumor cells, and attenuated the promoting effect of SPN on cell proliferation, migration and invasion. Conclusion: Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.

scholarly journals MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5160
Author(s):  
Thomas J. Kalantzakos ◽  
Travis B. Sullivan ◽  
Thales Gloria ◽  
David Canes ◽  
Alireza Moinzadeh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Stage I ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Glcnac Transferase ◽  
The Impact

MicroRNAs (miRNAs) are non-coding post-transcriptional regulators of gene expression that are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in tumor progression. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors, including miR-424-5p, that are associated with an aggressive phenotype. We investigate the impact of this dysregulated miRNA and its protein target O-GlcNAc-transferase (OGT) to better understand the mechanisms behind aggressive stage I ccRCC. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of miR-424-5p and OGT. Cells were transfected with pre-miR-424-5p, a lentiviral anti-OGT shRNA, or were treated with the demethylating agent 5-Aza-2′-deoxycytidine. Cell proliferation was measured via MT cell viability assay. Cell migration and invasion were analyzed using Transwell assays. The expression of miR-424-5p was determined through qRT-PCR, while OGT protein expression was evaluated through Western blotting. The interaction between miR-424-5p and OGT was confirmed via luciferase reporter assay. The transfection of ccRCC cells with pre-miR-424-5p or anti-OGT shRNA significantly inhibited cell proliferation, migration, and OGT expression, while miR-424-5p also attenuated cell invasion. Addition of the demethylating agent significantly reduced cell proliferation, migration, invasion, and OGT expression, while significantly increasing the expression of miR-424-5p. Altogether, these findings suggest that epigenetic downregulation of miR-424-5p, which in turn augments OGT expression, contributes to the creation of aggressive forms of stage I ccRCC.

scholarly journals Long noncoding RNA lnc-DILC stabilizes PTEN and suppresses clear cell renal cell carcinoma progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Han Zhang ◽  
Pengtao Wei ◽  
Wenwei Lv ◽  
Xingtao Han ◽  
Jinhui Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Liver Cancer ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Mechanistic Investigation

Abstract Background Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are crucial regulators affecting the progression of human cancers. Recently, lncRNA downregulated in liver cancer stem cells (lnc-DILC) was identified to function as a tumor suppressor inhibiting the tumorigenesis and metastasis in liver cancer and colorectal cancer. However, to date, little is known about the functional roles of lnc-DILC in modulating malignant phenotypes of clear cell renal cell carcinoma (ccRCC) cells. Methods lnc-DILC expression in human ccRCC tissues was detected by qRT-PCR. Overexpression and knockdown experiments were carried out to determine the effects of lnc-DILC on ccRCC cell proliferation, migration and invasion. To reveal the underlying mechanisms of lnc-DILC functions in ccRCC cells. RNA immunoprecipitation, RNA pull-down, in vivo ubiquitination, co-immunoprecipitation and western blot assays were performed. Results Here, we identified that lnc-DILC levels were dramatically downregulated in ccRCC tissues. Loss of lnc-DILC expression was correlated with larger tumor size, advanced tumor grade and lymph node metastasis, and also predicted worse prognosis in patients with ccRCC. Functionally, knockdown and overexpression experiments demonstrated that lnc-DILC inhibited cell proliferation, migration and invasion in ccRCC cells. Mechanistic investigation revealed that lnc-DILC bound to tumor suppressor PTEN and suppressed its degradation. lnc-DILC repressed the PTEN ubiquitination through blocking the interaction between PTEN and E3 ubiquitin ligase WWP2 and recruiting the deubiquitinase USP11 to PTEN. Moreover, we demonstrated that PTEN–AKT signaling was crucial for lnc-DILC-mediated suppressive effects. Conclusions In summary, our research revealed a novel mechanism by which lnc-DILC regulates PTEN stability via WWP2 and USP11, and shed light on potential therapeutic strategies by the restoration of lnc-DILC expression in patients with ccRCC.

scholarly journals miR-129-5p Inhibits Clear Cell Renal Cell Carcinoma Cell Proliferation, Migration and Invasion by Targeting SPN

2020 ◽  
Author(s):  
Bin Gao ◽  
Lijuan Wang ◽  
Yubo Zhang ◽  
Na Zhang ◽  
Miaomiao Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Regulated Expression ◽  
Ccrcc Cell

Abstract Objective: Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods: Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities.Results: miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Additionally, overexpressing miR-129-5p markedly reduced SPN expression in tumor cells, and attenuated the promoting effect of SPN on cell proliferation, migration and invasion.Conclusion: Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.

miR-155-5p Promotes Cell Proliferation and Migration of Clear Cell Renal Cell Carcinoma by Targeting PEG3

2021 ◽  
pp. 1-10
Author(s):  
Han Wu ◽  
Haixiao Wu ◽  
Peng Sun ◽  
Desheng Zhu ◽  
Min Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Promote Cell Proliferation

<b><i>Objective:</i></b> miR-155-5p as an important microRNA has been extensively studied for its biological functions and mechanisms in various cancers. However, the role and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain to be further elucidated. <b><i>Methods:</i></b> Bioinformatics methods were implemented to analyze differentially expressed genes in the cancer genome atlas database. qRT-PCR and Western blot were employed to detect the expression of miR-155-5p and paternally expressed gene 3 (PEG3) mRNA as well as protein expression. Cell lines with miR-155-5p knockdown or miR-155-5p/PEG3 co-overexpression were constructed. A series of experiments including the MTT method, wound healing assay, and transwell assay were carried out to detect the proliferation, migration, and invasion of cancer cells in different treatment groups. Bioinformatics analysis and dual-luciferase assay were conducted to confirm the targeting relationship between PEG3 and miR-155-5p in ccRCC. <b><i>Results:</i></b> miR-155-5p was found to be significantly upregulated in ccRCC cells, while PEG3 exhibited significantly low expression. The downregulation of miR-155-5p could inhibit cell proliferation, migration, and invasion of ccRCC. miR-155-5p could inhibit the expression of PEG3. The overexpression of miR-155-5p could promote cell proliferation, migration, and invasion, whereas overexpression of PEG3 could significantly attenuate such effect. Therefore, miR-155-5p may promote cell growth of ccRCC via inhibiting PEG3 expression. <b><i>Conclusion:</i></b> These findings validated the effect of miR-155-5p/PEG3 on ccRCC cells and provided novel potential targets for the prognosis and treatment of patients with ccRCC.

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.

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.

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