Demethylation drug 5-Aza-2′-deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro

Jiang, Juan; Yi, Bin; Sun, Jian; Cao, Wei; Liu, Mengzi

doi:10.3892/ol.2016.4364

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…35 Furthermore, Jiang J et al Has reported that increased expression of miR-200c inhibits the cell viability and EMT of clear cell renal cell carcinoma. 36 Therefore, we summarized the above points and scheduled the following plan of experiments that the highly related signaling pathway EMT should be taken into consideration for researches on CCRCC. What's more, one of the major limitations in this study was that all the mechanistic studies such as SLC6A1 knockdown and miR-200c-3p overexpression experiments were performed in only one cell line.…”

Section: Discussionmentioning

confidence: 99%

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

Maolakuerban

Azhati

Tusong

et al. 2018

Cancer Biology & Therapy

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In this study, we investigated the mechanism of miR-200c-3p and SLC6A1 in regulating cell activity of clear cell renal cell carcinoma (CCRCC). The mRNA and miRNA expressions of tissue specimens were analyzed by CapitalBio Corporation (Beijing, China). The expression of SLC6A1 in CCRCC cells was examined through qRT-PCR and western blot. The migration and invasion ability of 786-O cells was testified by transwell assay after transfected. 786-O cell proliferation ability was detected by MTT assay. Dual luciferase reporter assay verified the association between SLC6A1 and miR-200c-3p. SLC6A1 was high expressed and miR-200c-3p was low expressed in CCRCC tissues and cells. Besides, lower SLC6A1 expression indicated longer survival time and higher survival rate. MiR-200c-3p could directly target at SLC6A1 and reduce its expression. MiR-200c-3p inhibited the proliferation, migration and invasion in 786-O cells by down-regulating SLC6A1 expression. The results suggested that the miR-200c-3p served as a suppressor for CCRCC via down-regulating SLC6A1.

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Section: Discussionmentioning

confidence: 99%

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

Maolakuerban

Azhati

Tusong

et al. 2018

Cancer Biology & Therapy

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“…In RCC models, 5-Aza increased the expression of tumor suppressor genes like FBXW10, SMPD3, and Kank1 and thus suppress tumor cells growth and induce apoptosis [ 31 , 32 ]. 5-Aza treatment also can increase miR-200c, miR-492, and other miRNAs that have a suppressive role in epithelial-mesenchymal transition (EMT) and inhibit migration, invasion, and EMT in ccRCC cells [ 33 , 34 ]. Importantly, combining 5-Aza treatment with HDAC inhibitors results in a synergistic activation of silenced tumor suppressor genes, as well as synergistic antineoplastic effects on breast and lung carcinomas [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Valproic Acid and 5-Aza-2’-Deoxycytidine Synergistically Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration

Sun

et al. 2018

Med Sci Monit

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BackgroundHistone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2′-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P.Material/MethodsThe cell proliferation was detected by xCELLigence RTCA DP Instrument, viability by CCK8 assay, cell apoptosis and cell cycle by flow cytometry, and cell migration by wound healing assay, Transwell assay and xCELLigence RTCA DP Instrument.ResultsWe discovered that VPA and 5-Aza could individually induce decreased viability and have an inhibitory effect on the proliferation of 786-O and 769-P cells. This anti-growth effect was more pronounced when the cells were treated with both VPA and 5-Aza. The combination of VPA and 5-Aza also elicited more apoptosis and produced more cell cycle arrest in the G1 phase for both cell lines. On the other hand, treatment of RCC cells with VPA, 5-Aza, or a combination of both resulted in slow wound healing and impaired migration.ConclusionsThese findings clearly demonstrated that VPA combined with 5-Aza could significantly increase anti-RCC effects by inhibiting cellular proliferation, inducing apoptosis, promoting cell cycle arrest and prohibiting the migration of human RCC cells.

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“…Many of our top miRNAs, e.g., miR-122 [ 47 ], miR-200c [ 48 ] and miR-210 [ 49 ], have previously been linked to the epithelial–mesenchymal transition (EMT). In support of this, Lorens et al previously proposed EMT to be a central inducer of Axl expression [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives: Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma

Strauss

Marti

Beisland

et al. 2018

IJMS

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Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n = 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. In a comparison of tumour vs. normal, 182 miRNAs were found with significant differential expression; miR-155 was of particular interest as it classified all ccRCC samples correctly and correlated well with tumour size (R2 = 0.83); miR-155 also predicted poor survival with hazard ratios of 2.58 and 1.81 in two different TCGA (The Cancer Genome Atlas) datasets in a univariate model. However, in a multivariate Cox regression analysis including age, sex, cancer stage and histological grade, miR-155 was not a statistically significant survival predictor. In conclusion, formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA-sequencing material. Our results further support a role for miR-155 as a promising cancer classifier and potentially as a therapeutic target in ccRCC that merits further investigation.

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Demethylation drug 5-Aza-2′-deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro

Cited by 12 publications

References 27 publications

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

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

Combined Treatment with Valproic Acid and 5-Aza-2’-Deoxycytidine Synergistically Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration

Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives: Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma

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