Methylation profile of group of miRNA genes in clear cell renal cell carcinoma and their involvement in cancer progression

Береснева, Е. В.; Rykov, S. V.; Ходырев, Д. С.; Пронина, И. В.; Ермилова, В. Д.; Kazubskaya, T. P.; Брага, Э. А.; Логинов, В. И.

doi:10.1134/s1022795413030034

Cited by 23 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR-34b/c is involved in mediated cellular responses, such as cell cycle arrest (Yan et al, 2014), apoptosis, and metabolic regulation (Zhang et al, 2014). The reduced or deleted expression of miR-34b/c might contribute to diverse human cancers because of the aberrant CpG island methylation of its promoter (Beresneva et al, 2013;Nadal et al, 2013;Ng et al, 2014;Wu et al, 2014;Xie et al, 2014). However, only one study has reported the methylation of miR-34b/c gene promoters in STS cell lines and tissue samples (Vogt et al, 2011), but the methylation level of the miR-34b/c individual CpG unit and the exact function of DNA hypermethylation of miR-34b/c in STSs remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas

Xie

Zong

Wang

et al. 2015

Experimental and Molecular Pathology

View full text Add to dashboard Cite

Soft tissue sarcomas (STSs) are comparatively rare malignant tumors with poor prognosis. STSs predominantly arise from mesenchymal differentiation. MicroRNA-34b/c, the transcriptional targets of tumor suppressor p53, possesses tumor suppressing property. Hypermethylation of miR-34b/c has been associated with tumorigenesis and the progression of various cancers. To determine whether aberrant miR-34b/c methylation occurs in STSs, we quantitatively evaluated the methylation level of miR-34b/c in 57 STS samples and 20 cases of peripheral blood from healthy volunteers serving as normal controls by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. We found that miRNA34b/c is more frequently methylated in STSs (0.157±0.028) than in normal controls (0.098±0.012, p=0.038). Furthermore, the methylation levels of CpG_1.2.3, CpG_4.5.6.7, and CpG_11.12.13 of miR-34b/c were significantly higher in the STS group than in the normal control group (p<0.001). No significant differences in the methylation levels within miR-34b/c were observed between specific reciprocal translocations in STSs and nonspecific reciprocal translocations in STSs (0.146±0.039 vs. 0.168±0.035, p>0.05). The methylation levels of miR-34b/c in STSs were associated with clinical stage. The methylation levels of CpG_1.2.3, CpG_4.5.6.7, CpG_9.10, CpG_11.12.13, and CpG_14 in tumor-stage III/IV tissues were significantly higher than those in tumor-stage I/II tissues. Our findings indicated that DNA hypermethylation of the miR-34b/c is a relatively common event in STSs and is significantly correlated with late clinical stage in patients with STSs. Hypermethylation of the miR-34b/c may be pivotal in the oncogenesis and progression of STSs and may be a potential prognostic factor for STSs.

show abstract

Section: Introductionmentioning

confidence: 99%

Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas

Xie

Zong

Wang

et al. 2015

Experimental and Molecular Pathology

View full text Add to dashboard Cite

show abstract

“…Recently, enormous progress has been made in the discovery of microRNAs and in the evaluation of the DNA methylation effect on this new class of small noncoding RNAs. The methylation of miR9 genes has been studied in various solid cancers [14,15,16,17,18,19,20] and in some hematological malignancies, particularly leukemia [13,21], but, according to our knowledge, no previous study has reported the methylation status of miR9 loci in HL.…”

Section: Discussionmentioning

confidence: 83%

“…There are 3 genomic loci that code for the same mature miR9 : miR9-1 (1q22), miR9-2 (5q14.3) and miR9-3 (15q26.1) [13]. miR9 has frequently been silenced by hypermethylation in several types of human cancers, including gastric cancer [14], hepatocellular carcinoma [15], breast cancer [16], bladder cancer [17], small-cell lung cancer [18], oral and oropharyngeal squamous-cell carcinoma [19], renal-cell carcinoma [20] and leukemia [13,21]. …”

Section: Introductionmentioning

confidence: 99%

Investigation of miR9-1, miR9-2 and miR9-3 Methylation in Hodgkin Lymphoma

Dhiab

Ziadi²,

Louhichi³

et al. 2015

Pathobiology

View full text Add to dashboard Cite

Background: miR9 is an important tumor suppressor microRNA regulated by DNA methylation in various types of cancers. Methods: We analyzed the methylation status of the 3 members of the miR9 family in 58 cases of Hodgkin lymphoma (HL) in comparison to 15 reactive lymph nodes. We also assessed the relationships between miR9 methylation and Epstein-Barr virus (EBV) infection and several clinicopathological parameters. Results: We found that 84.5% of HL cases had a methylation in at least 1 of the 3 loci of miR9, whereas none of the nontumoral samples was methylated. The highest rate of methylation was found in miR9-2 (5q14.3) in 74.1% of the HL cases, followed by miR9-3 (15q26.1) in 56.9% and miR9-1 (1q22) in only 8.6% (p < 0.001). The promoter methylation of miR9-3 was more frequent in patients older than 15 years than in children (p = 0.02) and among women rather than men (p = 0.02). However, no significant correlation was found between miR9 methylation and EBV infection. Conclusion: These results indicate that miR9 methylation, especially miR9-2, is a frequent event in HL and may be involved in HL pathogenesis, irrespective of EBV infection.

show abstract

“…The 3'-UTRs of the wild-type and mutant eEF2K sequences were cloned into the PsiCHECK-2 Vector (Promega Corporation, Madison, WI, USA), as previously described (12). A Fast Mutagenesis System mutation kit (TransGen Biotech, Inc., Beijing, China) was used for mutant construction, and DNA sequences were confirmed by DNA sequencing.…”

Section: Rna Extraction and Reverse Transcription-quantitative Polymementioning

confidence: 99%

“…miRNAs are a group of small RNAs ~22 nucleotides in length that negatively regulate gene expression by binding to the 3'-untranslated region (3'-UTR) of the target mRNAs (11,12). miRNAs are involved in the regulation of cell proliferation, development, differentiation and apoptosis (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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

Shi

Liu

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

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.

show abstract

Methylation profile of group of miRNA genes in clear cell renal cell carcinoma and their involvement in cancer progression

Cited by 23 publications

References 28 publications

Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas

Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late clinical stage in patients with soft tissue sarcomas

Investigation of miR9-1, miR9-2 and miR9-3 Methylation in Hodgkin Lymphoma

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

Contact Info

Product

Resources

About