Microarray analysis of microRNA expression in renal clear cell carcinoma

Huang, Yi; Dai, Yong; Yang, Juhua; Chen, Ting-Wen; Yin, Yuan; Tang, Min; Hu, Chaofeng; Zhang, L.

doi:10.1016/j.ejso.2009.04.010

Cited by 78 publications

(58 citation statements)

References 25 publications

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“…The expression levels of miR-877 were observed to be downregulated in the RCC specimens, whereas the expression levels of its target gene eEF2K were upregulated in these samples. This trend has also been previously reported in other types of cancer, which suggests that miRNAs may be involved in the development of metastatic RCC (33,34).…”

Section: Discussionsupporting

confidence: 60%

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

Shi

Liu

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are involved in tumorigenesis. However, little is known about their role in renal cell carcinoma (RCC). In the present study, the function of the miRNA miR-877 in RCC was investigated, and its expression levels in blood and paired RCC tissues were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis predicted eukaryotic elongation factor-2 kinase (eEF2K) to be the potential mRNA target of miR-877, which was verified by luciferase assay. The expression levels of eEF2K in RCC tissues were evaluated by western blot analysis and qPCR. The proliferation and migration abilities of RCC cells were measured by MTT and in vitro wound healing assays, respectively. The present results indicated that the expression levels of miR-877 were downregulated in blood and paired RCC tissues, whereas the expression levels of eEF2K were upregulated in RCC tissues. In addition, overexpression of miR-877 and knockdown of eEF2K significantly reduced the proliferation and migration abilities of RCC cells in vitro. Furthermore, miR-877 affected the eEF2K/eEF2 signaling pathway in these cells. In conclusion, the present study has demonstrated that miR-877 suppresses the proliferation and migration abilities of RCC cells by modulating the eEF2K/eEF2 signaling cascade. Therefore, miR-877 may be considered a potential biomarker for the diagnosis of RCC.

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Section: Discussionsupporting

confidence: 60%

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

Shi

Liu

et al. 2015

Oncology Letters

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“…Of note, more mi RNAs were downregulated or silenced in renal tumours than in normal tissue, and this downregulation or silencing [Au: OK?] was often associated with promoter methylation or copy number changes 179,[182][183][184][185][186][187][188] . Many of these mi RNAs target components of networks that are dysregulated by mutations or promoter methylation.…”

Section: Bap1mentioning

confidence: 99%

The epigenetic landscape of renal cancer

2016

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| The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers.

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“…These data provides new insights into the molecular mechanisms underlying carcinogenesis (8,9). Aberrant RCC-specific miRNA profiles have been previously noted; however, no consensus has been reached on the significance of certain miRNAs in RCC (10)(11)(12)(13)(14)(15)(16)(17)(18). Among these dysregulated miRNAs, four members of miR-200s (miR-141, -200c, -200b, and -429) were all markedly downregulated in ccRCC tissues.…”

Section: Introductionmentioning

confidence: 99%

miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma

Wang

Chen

Wang

et al. 2015

Molecular Cancer Research

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miRNA expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. In this study, miRNA expression profiles were determined in clear cell renal cell carcinomas (ccRCC) and in matched normal kidney tissues by using a miRNA microarray platform which covers a total of 851 human miRNAs. Differential expression of 74 miRNAs were identified between ccRCC specimens and their matched adjacent noncancerous tissues, of which 30 were significantly upregulated in ccRCCs, and the other 44 were downregulated (fold change ! 2, P < 0.05). Interestingly, miR-200c was commonly downregulated in ccRCC specimens and ccRCC cell lines with significant functional consequences. Growth curve and FACS assay indicated that overexpression of miR-200c suppressed cell growth and induced cell-cycle arrest at G 0 -G 1 phases in SN12-PM6 and 786-O cells. Furthermore, miR-200c could suppress in vivo tumor growth of SN12-PM6 cells in mice. Bioinformatics exposed cyclin-dependent kinase 2 (CDK2) as a potential target of miR-200c, which was validated using a luciferase reporter assay. Mechanistic investigations revealed that miR-200c was directly responsible for suppressing the expression of CDK2 in ccRCC cell lines and xenografts. Taken together, miR-200c plays an antioncogenic role in ccRCC, through controlling cell growth and cell-cycle progression by downregulating the G 1 -S regulator CDK2.Implications: miR-200c exerts its novel antioncogenic function in renal cell carcinoma by controlling CDK2-dependent cell growth and cell-cycle progression.

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Microarray analysis of microRNA expression in renal clear cell carcinoma

Cited by 78 publications

References 25 publications

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma

The epigenetic landscape of renal cancer

miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma

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