scholarly journals LncRNA SNHG17 Promotes Tumor Progression and Predicts Poor Survival in Human Renal Cell Carcinoma via Sponging miR-328-3p

2020 ◽  
Author(s):  
Jie Wu ◽  
Gang Dong ◽  
Tingting Liu ◽  
Shaojin Zhang ◽  
Lulu Sun ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sequencing Data ◽  
Luciferase Reporter Gene ◽  
Clinicopathologic Characteristics ◽  
Human Renal Cell Carcinoma

Abstract Background: Accumulating data shows that dysregulation of long non-coding RNAs (lncRNAs) are involved in human tumors' occurrence and progression. Small nucleolar RNA host genes (SNHGs) are recently revealed to play a carcinogenic role in various human neoplasms. However, the functions and underlying mechanisms of lncRNA SNHG17 in renal cell carcinoma (RCC) are still elusive.Methods: We analyzed the relationship between SNHG17 expression levels and clinicopathologic characteristics and prognosis in patients with RCC according to TCGA RNA-sequencing data and our cohort data. Loss-of-function and gain-of-function experiments were conducted to examine the biological behaviors of SNHG17 on RCC cell proliferation, migration, invasion, apoptosis, and tumor growth in vivo. The interaction between SNHG17, miR-328-3p, and Histone’s H2A variant (H2AX) was verified by bioinformatics, dual-luciferase reporter gene, and RNA immunoprecipitation (RIP). Results: Highly expressed SNHG17 was evident in RCC tissue samples and cell lines, and SNHG17 overexpression was related to advanced TNM stage and reduced relapse-free and overall survival of patients with RCC. Knockdown of SNHG17 prohibited malignant phenotypes, whereas ectopic SNHG17 expression showed the opposite effects. More importantly, SNHG17 could upregulate the expression of H2AX by acting as a miR-328-3p sponge. In vivo experiments confirmed that SNHG17 promoted the growth of RCC tumors.Conclusion: SNHG17/miR-328-3p/H2AX axis might be involved in RCC progression, which provided a potential therapeutic target for RCC.

scholarly journals Tumor promoting effects of circRNA_001287 on renal cell carcinoma through miR-144-targeted CEP55

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jiafu Feng ◽  
Yongcan Guo ◽  
Yuanmeng Li ◽  
Jiawei Zeng ◽  
Yaodong Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Biological Activities ◽  
Potential Effect ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Subsequent Investigation

Abstract Background Renal cell carcinoma (RCC) is a common urological cancer. circular RNAs (circRNAs) is involved in the development of various types of cancers. However, the roles and underlying mechanisms of circRNAs in RCC are not fully elucidated. Herein, we aimed to examine the potential effect of circ_001287 on RCC progression. Materials and Methods Microarray-based gene expression profiling of RCC was initially employed in order to identify differentially expressed genes. Next, the expression of circ_001287 was examined, and the cell line with the highest circ_001287 expression was selected for subsequent investigation. The interaction among circ_001287, miR-144, and CEP55 was identified by conducting luciferase reporter assay, RNA-pull down, RIP, RT-qPCR and FISH. The effect of circ_001287 on proliferative, invasive and migratory capacities as well as tumorigenicity of transfected cells in mice was examined using gain- and loss-of-function experiments. Results circ_001287 and CEP55 were highly expressed while miR-144 was decreased in RCC tissues and cell lines. circ_001287 can up-regulate CEP55 by binding to miR-144, which resulted in increased proliferative, invasive and migratory capacities and tumor growth in vivo. In addition, down-regulation of miR-144 was also observed to promote these biological activities. Conclusions Overall, these results elucidate a new mechanism for circ_001287 in RCC development and provide a potential therapeutic target for RCC patients.

scholarly journals RASA1 inhibits the progression of renal cell carcinoma by decreasing the expression of miR-223-3p and promoting the expression of FBXW7

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Rui-Li Zhang ◽  
Ainiwaer Aimudula ◽  
Jiang-Hong Dai ◽  
Yong-Xing Bao
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

Abstract RAS p21 protein activator 1 (RASA1), also known as p120-RasGAP, is a RasGAP protein that functions as a signaling scaffold protein, regulating pivotal signal cascades. However, its biological mechanism in renal cell carcinoma (RCC) remains unknown. In the present study, RASA1, F-box/WD repeat-containing protein 7 (FBXW7), and miR-223-3p expression were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Then, the targeted correlations of miR-223-3p with FBXW7 and RASA1 were verified via a dual-luciferase reporter gene assay. CCK-8, flow cytometry, and Transwell assays were implemented independently to explore the impact of RASA1 on cell proliferation, apoptosis, migration, and cell cycle progression. Finally, the influence of RASA1 on tumor formation in RCC was assessed in vivo through the analysis of tumor growth in nude mice. Results showed that FBXW7 and RASA1 expression were decreased in RCC tissues and cell lines, while miR-223-3p was expressed at a higher level. Additionally, FBXW7 and RASA1 inhibited cell proliferation but facilitated the population of RCC cells in the G0/G1 phase. Altogether, RASA1 may play a key role in the progression of RCC by decreasing miR-223-3p and subsequently increasing FBXW7 expression.

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

188 Development of a realistic in vivo bone metastasis model for human renal cell carcinoma

2014 ◽  
Vol 13 (1) ◽  
pp. e188
Author(s):  
M.P. Valta ◽  
H. Zhao ◽  
A. Ingels ◽  
A.E. Thong ◽  
R. Nolley ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastasis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Human Renal Cell Carcinoma ◽  
Metastasis Model

scholarly journals LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuo Ye ◽  
Jiachen Duan ◽  
Lihui Wang ◽  
Yanli Ji ◽  
Baoping Qiao
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear. Methods LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay. Results LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors. Conclusion These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.

RNA-BINDING PROTEIN HUR BLOCKADE HAS POTENT ANTI-TUMOR ACTIVITIES IN HUMAN RENAL CELL CARCINOMA BOTH IN VITRO AND IN VIVO

2009 ◽  
Vol 181 (4S) ◽  
pp. 153-153 ◽  
Author(s):  
Sabrina Danilin ◽  
Lionel Thomas ◽  
Thomas Charles ◽  
Carole Sourbier ◽  
Véronique Lindner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Human Renal Cell Carcinoma

scholarly journals MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

2017 ◽  
Vol 43 (6) ◽  
pp. 2405-2419 ◽  
Author(s):  
Changlin Wang ◽  
Licheng Cai ◽  
Jing Liu ◽  
Gang Wang ◽  
Haoming Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Gene Expression Omnibus ◽  
Negative Regulator ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma

Background/Aims: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. Methods: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. Conclusion: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.

scholarly journals VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Science ◽  
2018 ◽  
Vol 361 (6399) ◽  
pp. 290-295 ◽  
Author(s):  
Jing Zhang ◽  
Tao Wu ◽  
Jeremy Simon ◽  
Mamoru Takada ◽  
Ryoichi Saito ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Nuclear Factor Κb ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma ◽  
A Genome

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.

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