scholarly journals Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N6-methyladenosine of PARP1 mRNA and downregulating PTEN

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lei Yang ◽  
Yi Chen ◽  
Ning Liu ◽  
QianCheng Shi ◽  
Xiaodong Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Rna Immunoprecipitation ◽  
Direct Binding ◽  
Xp11.2 Translocation ◽  
Novel Target

Abstract Background NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood. Methods FISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry. Results The expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N6-methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN. Conclusions TRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.

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 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-224-5p Targeting OCLN Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells

2021 ◽  
pp. 1-10
Author(s):  
Yifei Liu ◽  
Honglin Nie ◽  
Yubo Zhang ◽  
Na Zhang ◽  
Miaomiao Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Physiological Role ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Ccrcc Cell

A number of studies reported that miR-224-5p is involved in a variety of cancer-related cellular processes, yet its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. In order to clarify the function of miR-224-5p in ccRCC, real-time quantitative-PCR was conducted to compare the expression of miR-224-5p in human normal renal tubular epithelial cell lines and ccRCC cell lines first, and a strikingly upregulated expression was observed in ccRCC cell lines. Inhibition of miR-224-5p expression by microRNA inhibitors could inhibit the proliferation, migration, and invasion of ccRCC cells. Besides, it was validated by dual-luciferase assay in which miR-224-5p directly targeted OCLN gene. The expression of OCLN was downregulated in ccRCC cells, and overexpression of miR-224-5p could inhibit the mRNA and protein expression levels of OCLN. Overexpression of OCLN could reduce the proliferation, migration, and invasion of ccRCC cells, while overexpressed miR-224-5p could partially reverse that inhibitory effect. Therefore, the promotive effect of miR-224-5p on the proliferation, invasion, and migration of ccRCC cell lines was at least partly due to the inhibition of OCLN expression. These findings highlighted the important function of miR-224-5p, which was promoting cell proliferation, migration, and invasion by downregulating OCLN, in the pathogenesis of ccRCC, and provided a potential treatment strategy.

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.

Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

2016 ◽  
Vol 27 (2) ◽  
pp. 543-552 ◽  
Author(s):  
Xiao Chen ◽  
Qingqiang Zhu ◽  
Baoxin Li ◽  
Wenjing Cui ◽  
Hao Zhou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Gene Fusion ◽  
Fusion Imaging ◽  
Imaging Findings ◽  
Xp11.2 Translocation

scholarly journals Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Meng ◽  
Luojin Zhang ◽  
Mingjun Zhang ◽  
Kaiqin Ye ◽  
Wei Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Functional Enrichment ◽  
Cancer Tissue ◽  
Down Regulation

Abstract Background BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. Methods Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. Results BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients’ gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. Conclusions Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

Sign in / Sign up

Export Citation Format

Share Document