In vivo screens using a selective CRISPR antigen removal lentiviral vector system reveal immune dependencies in renal cell carcinoma

Immunity ◽  
2021 ◽  
Author(s):  
Juan Dubrot ◽  
Sarah Kate Lane-Reticker ◽  
Emily A. Kessler ◽  
Austin Ayer ◽  
Gargi Mishra ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Lentiviral Vector ◽  
Vector System ◽  
Antigen Removal

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.

Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells

Tumor Biology ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 551-559 ◽  
Author(s):  
Minoru Kobayashi ◽  
Tatsuo Morita ◽  
Nicole A. L. Chun ◽  
Aya Matsui ◽  
Masafumi Takahashi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Metastatic Potential ◽  
Host Immunity ◽  
In Vivo Models ◽  
Metastatic Behavior

scholarly journals Resistance after Chronic Application of the HDAC-Inhibitor Valproic Acid Is Associated with Elevated Akt Activation in Renal Cell Carcinoma In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53100 ◽  
Author(s):  
Eva Juengel ◽  
Jasmina Makarević ◽  
Igor Tsaur ◽  
Georg Bartsch ◽  
Karen Nelson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Valproic Acid ◽  
Cell Carcinoma ◽  
Hdac Inhibitor ◽  
Renal Cell ◽  
Akt Activation

scholarly journals MicroRNA-373 promotes tumorigenesis of renal cell carcinoma in vitro and in vivo

2017 ◽  
Vol 16 (5) ◽  
pp. 7048-7055 ◽  
Author(s):  
Yanli Li ◽  
Da Zhang ◽  
Jiaxiang Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell

scholarly journals circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Ling Gao ◽  
Xian Shao ◽  
Qingqing Yue ◽  
Weifei Wu ◽  
Xuejuan Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Therapeutic Strategy ◽  
Underlying Mechanism ◽  
Tumor Stage ◽  
Circular Rnas ◽  
The Novel ◽  
Regulatory Functions

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.

scholarly journals ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglin Gao ◽  
Lei Gao ◽  
Simin Wang ◽  
Xiaokai Shi ◽  
Chuang Yue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Invasion Assay ◽  
Cell Renal Cell Carcinoma ◽  
Atf3 Expression

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence has shown that ATF3 is associated with tumor progression.MethodsUsing qPCR, the expression of ATF3 was detected in 93 patients with ccRCC, including 24 paired normal and tumor tissues, which were used to further compare ATF3 expression through western blotting and immunohistochemistry. Lentivirus was used for the overexpression or knockdown of ATF3, and the consequent alteration in function was analyzed through CCK8 assay, colony formation assay, wound healing assay, invasion assay, and flow cytometry. The potential mechanism affected by ATF3 was analyzed through gene set enrichment analysis (GSEA) and verified using western blotting, invasion assay, or immunofluorescence staining. Furthermore, a xenograft mouse model was used to assess the function of ATF3 in vivo.ResultsATF3 expression was significantly decreased in ccRCC compared to that in adjacent normal tissues. Through gain- and loss-of-function experiments performed in an in vitro assay, we found that ATF3 could regulate ccRCC cell proliferation, cycle progression, migration, and invasion. In the in vivo study, the xenograft mouse model revealed that ATF3 overexpression can inhibit the growth of ccRCC. Moreover, the mechanism analysis showed that suppression of ATF3 could lead to an increase the expression of β-catenin and promote β-catenin transfer to the nucleus, and might be affected by EGFR/AKT/GSK3β signaling.ConclusionATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategies for ccRCC include targeting the ATF3/EGFR/AKT/GSK3β/β−catenin signaling pathway.

scholarly journals Does Fingolimod have anticancer effects? A meta-analysis and systematic review based on experimental animal models of various cancers

2020 ◽  
Author(s):  
Yuze Ge ◽  
Ping Zhou ◽  
Lu Kong
Keyword(s):  
Renal Cell Carcinoma ◽  
Animal Models ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Meta Analysis ◽  
Signal Pathways ◽  
Bias Analysis ◽  
Immunodeficient Mice ◽  
Anticancer Effects

Abstract Background: Numerous studies have explored the anticancer effect of FTY720 (Fingolimod) in animal models, a sphingosine-1-phosphate (S1P) receptor antagonist and an immunosuppressant, but little clinical evidence guides the use of FTY720 in cancer patients.Methods: Strictly, only related published articles about the treatment with FTY720 for various cancers in vivo from January 1998 to January 2020 were selected from PubMed, Web of Science, Ovid, Embase, CNKI and Cochrane databases, and which were qualified. We acquired agreement through discussion. Then, we conducted meta-analysis, subgroups analysis, publication bias analysis and sensitivity analysis based on selected studies. In the last two sections, we summaried and compared side effects, drug combination effects and molecular pathways from selected studies.Results: In the 31 articles included from 2002 to 2019, FTY720 was found to reduce tumor volume (SMD =-2.58, 95% CI: -3.42, -1.75, Z = 6.09, P = 0.000), tumor weight (SMD = -3.69, 95% CI: -5.17, -2.21, Z = 4.88, P = 0.000) and body weight (SMD = -0.86, 95% CI: -1.61, -0.11, Z = 2.23, P = 0.025) in 14 types of cancer. Relevant frequent signal pathways include the Akt pathway, S1PRs-Caspase pathway and the STAT3-PP2A pathway. FTY720 has significant independent or in combination anticancer effects and a lower toxicity in renal cell carcinoma and neuroblastoma mice models. However, it should be noted that FTY720 achieved a significant therapeutic effect in immunodeficient mice, not in immunecompetent mice. Also, the dosage-safety of FTY720 alone in clinical use is a noteworthy issue. In mouse models, the mechanism of the FTY720 treatment of tumors lies in inducing the tumor cells apoptosis through important signaling moleculars.Conclusions: FTY720 alone or in combination exerted significant anti-tumor effects for neuroblastoma and renal cell carcinoma, however not for melanoma. Due to insufficient evidence, more specific studies of FTY720 only and in combination included in immunity, inflammation and melanoma should be carried out in the future preclinical and clinical studies.

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