scholarly journals Circular RNA ITCH Is a Tumor Suppressor in Clear Cell Renal Cell Carcinoma Metastasis through miR-106b-5p/PDCD4 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ping Gao ◽  
Yong Huang ◽  
Yanmei Hou ◽  
Qian Li ◽  
Haimei Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma

High metastasis of clear cell renal cell carcinoma (ccRCC) significantly influenced survival rate of ccRCC patients. Here, we intended to investigate the impacts of circular RNA ITCH (circ-ITCH) on the metastasis of ccRCC. The expression of circ-ITCH in ccRCC tissues and cells was evaluated utilizing qRT-PCR. Transwell assay and wound healing were applied to investigate migration and invasion of ccRCC cells. Target gene prediction and screening and luciferase reporter gene assays were utilized to assess downstream target genes of circ-ITCH. Western blot was utilized to detect metastasis-related protein expression. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. Results showed that circ-ITCH was low expressed in ccRCC tissues and cells. Downregulation circ-ITCH promoted cell migration, but overexpressing circ-ITCH inhibited cell migration and invasion in OSRC-2 and SW839 cells. Mechanism investigations claimed that circ-ITCH exerted its metastasis-inhibitory activity via sponging miR-106b-5p and regulating the expression of PDCD4. Conclusively, circ-ITCH suppresses ccRCC metastasis by enforcing PDCD4 expression through binding miR-106b-5p. circ-ITCH may function as a novel diagnostic target to suppress ccRCC metastasis.

scholarly journals Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Dingwei Xue ◽  
Huan Wang ◽  
Yuanlei Chen ◽  
Danyang Shen ◽  
Jieyang Lu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
E Cadherin

Abstract Background Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. Methods We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. Results Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. Conclusion Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.

TRIM13 inhibits cell migration and invasion in clear-cell renal cell carcinoma

2019 ◽  
Vol 72 (7) ◽  
pp. 1115-1124 ◽  
Author(s):  
Hualei Li ◽  
Lili Qu ◽  
Rui Zhou ◽  
You Wu ◽  
Shujun Zhou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Cell Migration And Invasion

scholarly journals MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1

2018 ◽  
Vol 19 (4) ◽  
pp. 282-291 ◽  
Author(s):  
Naibijiang Maolakuerban ◽  
Baihetiya Azhati ◽  
Hamulati Tusong ◽  
Asimujiang Abula ◽  
Anniwaer Yasheng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Cell Migration And Invasion

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.

Exploiting Synthetic Lethal Network for Precision Treatment of Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Zhicheng Liu ◽  
Dongxu Lin ◽  
Linmeng Zhang ◽  
Chen Yang ◽  
Bin Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Large Scale ◽  
Target Genes ◽  
Clear Cell ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Treatment Modalities ◽  
Cell Renal Cell Carcinoma

Abstract Background The emerging of targeted therapies has revolutionized the treatment modalities of advanced clear cell renal cell carcinoma (ccRCC) over the past fifteen years. However, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles of ccRCC cohorts were exploited for conducting an integrative analysis. Method Based on synthetic lethality (SL), a concept that simultaneous losses of two genes cause cell death while a single loss does not, we sought to develop a computational pipeline to infer potential SL partners of ccRCC. Drug response prediction were received from three pharmacological databases to select agents which are likely to be effective in precisely treating patients with target gene mutation. Results We developed a credible method to identify SL pairs and determined a list of 72 candidate pairs which might be utilized to selectively eliminate tumors with genetic aberrations through SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medicine targets for patients with BAP1 mutations. After mapping these target genes to comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potential in BAP1 mutant tumors. Conclusion Overall, our findings provide insight into the overview of ccRCC mutation patterns and offer novel opportunities for improving individualized cancer treatment.

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.

scholarly journals 8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeanette E. Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew L. Kosel ◽  
Daniel Serie ◽  
Paul A. Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas. Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR = 1.6, p = 0.0037) and SSIGN score (OR = 1.9, p = 0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

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