Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Zhu, Jing; Yang, Lifen; Xu, Ye; Lu, Mingzhu; Liu, Yongping; Zhang, Changsong

doi:10.3892/ol.2017.5656

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…The different patterns of DNA methylation and their values as potential biomarkers for diagnoses and prognoses in many cancer cells have been studied in pancreatic cancer, [16,17] peripheral T-cell lymphoma, [3] breast cancer, [18] and esophageal squamous cell carcinoma. [19] The hypermethylated pattern of RECK gene promoter is also reported in many cancers such as non-small-cell lung carcinoma, colorectal, pancreas, and stomach cancers as well as HCC, [2] concordant with results obtained in the current study.…”

Section: Resultssupporting

confidence: 91%

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients

El-Khair

Elalfy

Diasty

et al. 2021

J Biochem & Molecular Tox

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The RECK gene, a tumor suppressor gene, inhibits angiogenesis, invasion, and tumor metastasis. Epigenetic regulation of the RECK gene constitutes a potent approach to the molecular basis of liver malignancy. This study aims to evaluate the promoter methylation status of the RECK gene and its serum level in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and the potential association of RECK gene methylation with clinical criteria of HCC. One hundred and fifty-five subjects were included (healthy control [55], chronic HCV patients [55], HCV-related HCC patients [45]). The methylation status of the RECK gene promoter and serum RECK level were investigated by methylation-specific PCR and enzyme-linked immunosorbent assay techniques, respectively. RECK gene promoter hypermethylation was recorded in 46.7% of HCC patients, and 10.9% of HCV patients, but not in control subjects (0%). It was related to RECK protein level, varices, edema, ascites, lymph node metastasis, vascular invasion, and the largest diameter of focal lesions. Meanwhile, it was not associated with focal lesion number nor distant metastasis of HCC. In conclusion, RECK gene promoter hypermethylation is linked to HCV genotype-4-related HCC. Moreover, different degrees of RECK gene promoter methylation are associated with serum RECK level, lymph node metastasis, and vascular invasion, which could prove its pathogenic role in hepatocarcinogenesis in chronic HCV-infected patients.

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Section: Resultssupporting

confidence: 91%

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients

El-Khair

Elalfy

Diasty

et al. 2021

J Biochem & Molecular Tox

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“…[27][28][29][30] On the other hand, the association of RECK promoter hypermethylation with poor survival for patients with tumor was also uncovered. [31][32][33] For the validation of our speculation, the qRT-PCR analysis was utilized. As examined, the expression of RECK was significantly depleted in HPV-positive CC cells ( Figure 2C).…”

Section: Snhg8 Is Primarily Nuclear and Impedes Reck Expressionmentioning

confidence: 99%

LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV‐induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression

Wang

et al. 2020

J of Cellular Biochemistry

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Infection of human papillomaviruses (HPVs), such as subtypes HPV16 and HPV18 is carcinogenic to human and is prominent cause of HPV‐positive cervical carcinoma (CC). A closer investigation into the mechanism of HPV‐induced CC may stimulate the generation of an improved therapy treating cervical cancer. Our study herein interrogated the function of a small nucleolar RNA host gene 8 (SNHG8) in HPV‐induced CC. As a result, a notable increase of SNHG8 in HPV‐induced CC cells was found compared with HPV‐negative CC cells. Functionally, it identified that SNHG8 aggravated the cell proliferation and migration in Cell Counting Kit‐8 and transwell assays. Besides, flow cytometry apoptosis assay displayed that blockade of SNHG8 exacerbated apoptosis of HPV‐positive CC cells. As detected by fluorescence in situ hybridization analysis and subcellular fractionation assay, SNHG8 was primarily expressed in the nucleus and exerted suppressive role on reversion inducing cysteine‐rich protein with kazal motifs (RECK) expression, which implied a potential transcriptional regulation of SNHG8 on RECK level. Mechanically, SNHG8 was disclosed to interact with enhancer of zeste homolog 2 (EZH2) based on RNA immunoprecipitation assay. ChIP assay further unveiled the occupancy of EZH2 in the promoter region of RECK. An additional chromatin immunoprecipitation assay highlighted that SNHG8 intensified the enrichment of EZH2 and H3K27me3 in RECK promoter region. Altogether, it reflected that SNHG8 recruited EZH2 to downregulate RECK expression, leading to HPV‐induced CC aggravation.

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“…If a therapeutic means of enhanceing RECK expression is developed, it may be valuable in improving prognosis and impeding tumor progression. Another theory regarding RECK relates to hypoxic microenvironments, which interact with hypoxia-inducible factor (HIF)-1 α prompting RECK downregulation with histone deacetylase (HDAC)1 to silence the RECK gene ( Zhu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential genes in upper tract urothelial carcinoma using next-generation sequencing with bioinformatics and in vitro analyses

Lee

et al. 2021

PeerJ

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Background We aimed to identify prognostic biomarkers of upper tract urothelial carcinomas (UTUCs), including microRNAs (miRNAs) and genes which account for only 5% to 10% of all urothelial carcinomas (UCs). In Taiwan, this figure is markedly higher, where it can reach up to 30% of UC cases. Materials and Methods Using next-generation sequencing (NGS), we analyzed two pairs of renal pelvis tumors and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity® Pathway Analysis databases, we identified candidate genes. To search for upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study using western blot analysis and quantitative real-time reverse transcriptase-PCR. Results Interactions between selected target genes obtained using the NGS and miRmap methods were assessed through a Venn diagram analysis. Six potential genes, namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3 and CYBRD1 showed significant differences. Further analysis of gene expression from the GEO dataset indicated lower expression of PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumor suppressors in UTUC. In addition, we compared the expression of these genes in various UC cell lines (RT4, BFTC905, J82, T24, UMUC3, 5637, BFTC 909, UMUC14) and found decreased expression of PDE5A in muscle-invasive UC cells compared with the RT4 cell line. Furthermore, by using paired UTUC and normal tissues from 20 patients, lower PDE5A expression was also demonstrated in tumor specimens. Conclusions Our findings suggest these candidate genes may play some roles in UTUC progression. We propose that these markers may be potential targets clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumor suppressor genes, as identified by comparing the expression between normal and tumor specimens.

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Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

Cited by 10 publications

References 28 publications

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients

LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV‐induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression

Identification of potential genes in upper tract urothelial carcinoma using next-generation sequencing with bioinformatics and in vitro analyses

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