Predictive role of vascular endothelial growth factor polymorphisms in the survival of renal cell carcinoma patients

Yang, Yaojing; Chen, J.

doi:10.4238/2014.july.4.16

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…In ~33% of cases, patients with ccRCC are diagnosed with local or distant metastases due to its variable clinical presentation (7). In addition, there is a 40% recurrence rate in patients with ccRCC following surgery (8,9). Therefore, identifying novel therapeutic targets may improve the survival outcome and treatment response of patients with advanced ccRCC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang

et al. 2019

Exp Ther Med

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Recent studies have identified several microRNAs (miRNAs/miRs) that are dysregulated in clear cell renal cell carcinoma (ccRCC), and their dysregulation may serve important roles in the occurrence and development of ccRCC. Therefore, understanding the expression pattern and functional roles of miRNAs in ccRCC may facilitate the identification of novel therapeutic targets for the treatment of ccRCC. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-508 expression levels in ccRCC tissue samples and cell lines. The cell counting kit-8 and in vitro Transwell invasion assays were used to examine the effects of miR-508 overexpression on ccRCC cell proliferation and invasion, respectively. In addition, bioinformatics analysis and dual-luciferase reporter gene assays were used to investigate the underlying mechanism of miR-508 in ccRCC cells. Furthermore, the regulatory role of miR-508 on zinc finger E-box-binding homeobox 1 (ZEB1) mRNA and protein expression in ccRCC cells was investigated using RT-qPCR and western blot analysis, respectively. Additionally, the association between miR-508 and ZEB1 expression in ccRCC tissue samples was examined. Rescue experiments were performed to determine whether the tumor suppressive effects of miR-508 may be mediated by ZEB1 in ccRCC cells. The results of the current study demonstrated that miR-508 expression was significantly downregulated in ccRCC tissue samples and cell lines. In addition, miR-508 overexpression significantly decreased the proliferation and invasion of ccRCC cells. ZEB1 was identified as a direct target gene of miR-508 in ccRCC cells and the relative expression level of ZEB1 mRNA was significantly increased in ccRCC tissue samples. Furthermore, a negative correlation between miR-508 and ZEB1 expression was identified in ccRCC tissues. ZEB1 knockdown exhibited a functional role similar to miR-508 overexpression in ccRCC cells, and restoration of ZEB1 expression significantly reversed the inhibitory effects of miR-508 on the malignant phenotype of ccRCC cells. Taken together, the results of the current study demonstrated that miR-508 may serve a tumor suppressive role in ccRCC via direct targeting of ZEB1. MiR-508 may present a novel and efficient therapeutic target for the treatment of patients with ccRCC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang

et al. 2019

Exp Ther Med

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“…The most common sites of metastatic spread in RCC are the lung, bone, adrenal gland, liver and brain, whereupon more than one organ system is often involved in the metastatic process (3). In addition, RCC is relatively resistant to radiotherapy and chemotherapy, which result in the poor prognosis of patients with RCC with metastatic or recurrent disease and a 5-year survival rate of <20% (4). A number of studies have identified putative oncogenes involved in the carcinogenesis of RCC; however, the molecular mechanisms regulating the aggressive properties of RCC remain poorly understood (5,6).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA-204 inhibits cell proliferation, migration and invasion in human renal cell carcinoma cells by downregulating SOX4

Pan

Zhou

et al. 2015

Molecular Medicine Reports

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MicroRNA-204 (miR-204) has been reported to be frequently downregulated in various types of cancer, including renal, brain, ovary, hematological and colon cancer. The present study, investigated the effects of miR‑204 on renal cell carcinoma. Following transfection of miR‑204, an MTT assay, cell migration assay, cell invasion assay, western blot analysis and luciferase assay were performed in renal cell carcinoma cell lines. It was demonstrated that miR‑204 inhibits cell proliferation, migration and invasion in 786‑O and A498 cells. To the best of our knowledge, this study is the first to demonstrate that miR‑204 directly targets SOX4 in renal cell carcinoma. These results suggested that miR-204 may have value as a marker for the early detection of tumor metastasis and a therapeutic target preventing the invasion of renal cell carcinoma.

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“…It has previously been reported that ~33% of patients with ccRCC displayed metastasis at diagnosis, resulting in poor prognosis and a low 5-year survival rate (14). However, previous studies have demonstrated the prognosis of RCC improves when the expression of a number of genes is targeted, including Tim-3 (15,16).…”

Section: Discussionmentioning

confidence: 99%

Interference with Tim-3 protein expression attenuates the invasion of clear cell renal cell carcinoma and aggravates anoikis

Lü

Liu

et al. 2017

Molecular Medicine Reports

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Tumor cells resistant to anoikis are considered to be candidates for metastasis. In the present study, the role of Tim-3 in anoikis and its influence on the invasion of clear cell renal cell carcinoma (ccRCC) was investigated. Here, polyhydroxylethylmethacrylate (poly-HEMA) was applied to two ccRCC cell lines, 786-O and Caki-2, to induce detachment from the extracellular matrix (ECM). Tim-3 mRNA and protein expression levels were assayed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively. Anoikis was measured by Ho33342/PI double staining, acridine orange staining, and further determined using the CytoSelect™ 24-well Anoikis Assay kit. Apoptosis was measured using flow cytometry, E-cadherin and N-cadherin protein expression were determined using western blotting and a Chemicon cell invasion assay kit was used to quantify the invasive capacity of 786-O and Caki-2 cells. It was demonstrated that detachment from the ECM decreases transcription and the protein expression level of Tim-3 in 786-O and Caki-2 cells compared with control cells. Interference with Tim-3 expression using small interfering RNA exacerbated anoikis in 786-O and Caki-2 cells induced by poly-HEMA treatment. E-cadherin upregulation, N-cadherin downregulation, and ECM detachment-induced reduction in invasion ability were all exacerbated by knockdown of Tim-3. In conclusion, interference with Tim-3 expression may attenuate the invasion of renal cell carcinoma by aggravating anoikis, indicating Tim-3 as a potential therapeutic target for treating ccRCC.

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Predictive role of vascular endothelial growth factor polymorphisms in the survival of renal cell carcinoma patients

Cited by 12 publications

References 24 publications

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Upregulation of microRNA-204 inhibits cell proliferation, migration and invasion in human renal cell carcinoma cells by downregulating SOX4

Interference with Tim-3 protein expression attenuates the invasion of clear cell renal cell carcinoma and aggravates anoikis

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