Aberrant DNA methylation of ADAMTS16 in colorectal and other epithelial cancers

Kordowski, Felix; Kolarova, Julia; Schafmayer, Clemens; Buch, Stephan; Goldmann, Torsten; Marwitz, Sebastian; Kügler, Christian; Scheufele, Swetlana; Gaßling, Volker; Németh, Christopher Georg; Brosch, Mario; Lucius, Ralph; Röder, Christian; Kalthoff, Holger; Siebert, Reiner; Ammerpohl, Ole; Reiß, Karina

doi:10.1186/s12885-018-4701-2

Cited by 30 publications

(28 citation statements)

References 32 publications

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“…PENK is down-regulated and methylated in prostate, bladder, pancreatic, and colorectal cancers 28 ; however, its relationship in GC has not been explored. The ADAMTS family is thought to play an important role in carcinogenesis; however, the function and regulation of ADAMTS16 in carcinogenesis are not clearly defined 29 .…”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Kim

Jang

Heo

et al. 2020

Sci Rep

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Understanding cancer-prone environments is important to efficiently detect and prevent cancers. The associations between miRNA and cancer-prone environments are still largely unknown in gastric cancer (GC). Six miRNAs that are differentially expressed during gastric carcinogenesis were selected, and quantitative real-time pcR was performed in an independent training set (fresh non-tumor and tumor samples from 18 GC patients) and validation sets (set 1 with formalin-fixed paraffin-embedded non-tumor and tumor samples from 19 solitary GC and set 2 with 37 multiple GC patients). The results were compared with those of 37 gastric mucosa from 20 healthy volunteers. The expression levels of miR-26a, miR-375, and miR-1260 in gastric mucosa from healthy volunteers were statistically higher than that of non-tumorous gastric mucosa located 3 cm apart from the GC in the training set (miR-26a, P < 0.0001; miR-375, P = 0.0049; miR-1260, P = 0.0172), validation set 1 (miR-26a and miR-375, P < 0.0001; miR-1260, P = 0.0008), and validation set 2 (miR-26a, miR-375, and miR-1260, P < 0.0001). And a combination of miR-26a and miR-1260 showed the highest area under the curve value of 0.89. miRNAs are differentially expressed in non-neoplastic gastric mucosa and can be used as a biomarker to predict cancer-prone environments.

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Section: Discussionmentioning

confidence: 99%

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Kim

Jang

Heo

et al. 2020

Sci Rep

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“…STC2 was overexpressed in COAD, and its expression was positively correlated with the disease progression. Since many studies have shown that aberrant DNA methylation has a significant impact on gene expression and prognosis in some cancers[33,34], and a previous study reported that reducing the expression of DNA methyltransferase 1 could stimulate STC2 expression[35], we hypothesized that methylation might contribute to the overexpression of STC2. To verify this, the promoter DNA methylation data from TCGA Infinium HumanMethylation450K BeadChip arrays for COAD[36] were subjected to methylation analysis of the STC2 promoter.…”

Section: Resultsmentioning

confidence: 99%

Sp1 contributes to overexpression of stanniocalcin 2 through regulation of promoter activity in colon adenocarcinoma

Liu

Zhang

et al. 2019

WJG

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BACKGROUND Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the role of its overexpression in the development of COAD remains unclear. AIM To evaluate the regulation mechanism of STC2 overexpression in COAD. METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO (GSE50760). Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform, and the correlation between STC2 expression and survival rate was investigated with TCGA COAD. Transcription binding site prediction was conducted by TRANSFAC and LASAGNA, and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines, including HEK293T, NCM460, HT29, SW480, and HCT116. Western blotting was performed to evaluate the role of Sp1 on the expression of STC2. RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis. Importantly, the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2. A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2, and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2. Furthermore, inhibition of Sp1 remarkably decreased protein levels of STC2. CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity. Taken together, our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.

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“…Previous studies have explored the impact of DNA methylation events on lung tumor initiation and progression 19 - 22 , 27 - 29 , 66 - 68 . However, those studies mainly investigated a single gene or a small number of genes and a NGS-based methylation investigation in lung cancer has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance

Sun¹,

Yi²,

Yang³

et al. 2021

Theranostics

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Background: Aberrant DNA methylation occurs commonly during carcinogenesis and is of clinical value in human cancers. However, knowledge of the impact of DNA methylation changes on lung carcinogenesis and progression remains limited. Methods: Genome-wide DNA methylation profiles were surveyed in 18 pairs of tumors and adjacent normal tissues from non-small cell lung cancer (NSCLC) patients using Reduced Representation Bisulfite Sequencing (RRBS). An integrated epigenomic-transcriptomic landscape of lung cancer was depicted using the multi-omics data integration method. Results: We discovered a large number of hypermethylation events pre-marked by poised promoter in embryonic stem cells, being a hallmark of lung cancer. These hypermethylation events showed a high conservation across cancer types. Eight novel driver genes with aberrant methylation (e.g., PCDH17 and IRX1) were identified by integrated analysis of DNA methylome and transcriptome data. Methylation level of the eight genes measured by pyrosequencing can distinguish NSCLC patients from lung tissues with high sensitivity and specificity in an independent cohort. Their tumor-suppressive roles were further experimentally validated in lung cancer cells, which depend on promoter hypermethylation. Similarly, 13 methylation-driven ncRNAs (including 8 lncRNAs and 5 miRNAs) were identified, some of which were co-regulated with their host genes by the same promoter hypermethylation. Finally, by analyzing the transcription factor (TF) binding motifs, we uncovered sets of TFs driving the expression of epigenetically regulated genes and highlighted the epigenetic regulation of gene expression of TCF21 through DNA methylation of EGR1 binding motifs. Conclusions: We discovered several novel methylation driver genes of diagnostic and therapeutic relevance in lung cancer. Our findings revealed that DNA methylation in TF binding motifs regulates target gene expression by affecting the binding ability of TFs. Our study also provides a valuable epigenetic resource for identifying DNA methylation-based diagnostic biomarkers, developing cancer drugs for epigenetic therapy and studying cancer pathogenesis.

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Aberrant DNA methylation of ADAMTS16 in colorectal and other epithelial cancers

Cited by 30 publications

References 32 publications

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Sp1 contributes to overexpression of stanniocalcin 2 through regulation of promoter activity in colon adenocarcinoma

An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance

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