Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer

Wang, Hao; Xu, Man; Cui, Xiaobo; Liu, Yixin; Zhang, Yi; Sui, Yu; Wang, Dong; Peng, Lei; Wang, Dexu; Yu, Jingcui

doi:10.1038/srep21755

Cited by 14 publications

(13 citation statements)

References 27 publications

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“…EPB41L3 is extensively expressed in various human tissues. However, downregulation of EPB41L3 was frequently observed in cases of gastric cancer, non-small cell lung carcinoma cells and renal clear cell carcinoma [ 13 – 15 ]. This evidence suggests that EPB41L3 acts as a tumor suppressor in pathogenesis of these tumors.…”

Section: Introductionmentioning

confidence: 99%

LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p

et al. 2017

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Numerous studies have demonstrated that a class of long noncoding RNAs (lncRNAs) are dysregulated in hepatocellular carcinoma (HCC) and they are closely related with tumorigenesis. Our previous studies indicated that LINC00052 was a downregulated lncRNA in HCC and acted as a tumor suppressor gene. Using transcription microarray analysis, we found that knockdown of LINC00052 resulted in EPB41L3 downregulation. However, the function of EPB41L3 and the mechanism of LINC00052 downregulating EPB41L3 in HCC remain unclear. In this study, we found that overexpression of LINC00052 could upregulate the EPB41L3 expression and it might serve as a tumor suppressor gene in HCC. Database analysis showed that miR-452-5P could target LINC00052. The binding regions between LINC00052 and miR-452-5P were confirmed by luciferase assays. Moreover, LINC00052 inhibited cell malignant behavior by increasing miR-452-5P expression, suggesting that LINC00052 was negatively regulated by miR-452-5P. In addition, overexpression of miR-452-5P resulted in a decrease of EPB41L3 expression, suggesting that EPB41L3 was as a target of miR-452-5P. In conclusion, these results demonstrated that a novel pathway was mediated by LINC00052 in HCC.

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Section: Introductionmentioning

confidence: 99%

LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p

et al. 2017

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“…Epigenetic silencing of tumor-related genes due to CpG island methylation has been reported in GC, and is acknowledged as an important mechanism leading to early gastric tumorigenesis [ 17 , 27 , 28 ]. Although DNA methylation inhibitor 5-aza-dC can upregulate SHIP2 expression in GC cells, the result of BGS revealed promoter hypomethylation of INPPL1 in GC cells ( Figure 1 B,C).…”

Section: Discussionmentioning

confidence: 99%

Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells

Yan

Xue

Xiao

et al. 2017

IJMS

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Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis of gastric cancer cells. However, the mechanisms underlying the reduced expression of SHIP2 in gastric cancer remain unclear. While gene copy number variation analysis and exon sequencing indicated the absence of genomic alterations of SHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation of SHIP2 in gastric cancer cells. Analysis of transcriptional activity of SHIP2 promoter revealed Specificity protein 1 (Sp1) was responsible for the regulation of SHIP2 expression in gastric cancer cells. Furthermore, Sp1 expression, but not Sp3, was frequently downregulated in gastric cancer compared with normal gastric mucosa, which was associated with a paralleled reduction in SHIP2 levels in gastric cancer. Moreover, overexpression of Sp1 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, which was, at least in part, due to transcriptional activation of SHIP2 mediated by Sp1, thereby inactivating Akt. Collectively, these results indicate that decreased expression of transcription factor Sp1 contributes to suppression of SHIP2 in gastric cancer cells.

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“…In cancer cell genomes, abnormal DNA methylation is usually represented by global hypomethylation along with focal hypermethylation at promoter CpG islands (CGIs) of a number of tumor suppressor genes [2]. The malignant transformation of normal cells may be partially attributed to hypermethylation at promoters and aberrant expression of some tumor suppressor genes [3,4]. Synthetic DNA hypomethylating drugs, such as 5-azacytidine, 5-aza-2 ′ -deoxycytidine, zebularine, and others, are used in cancer treatments.…”

Section: Introductionmentioning

confidence: 99%

Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway

Tong

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Curcumin, a natural polyphenol antioxidant extracted from the root of turmeric (Curcuma longa), can induce apoptosis and DNA demethylation in several types of cancer cells. However, the mechanism of its anticancer potentials and DNA demethylation effects and the potential relationships between these outcomes have not been clearly elucidated. In the present study, the effects of curcumin on the proliferation, colony formation, and migration of human gastric cancer cells (hGCCs) were explored. Reactive oxygen species (ROS) levels, mitochondrial damage, DNA damage, and apoptosis of curcumin-treated hGCCs were analyzed. Changes in the expression of several genes related to DNA damage repair, the p53 pathway, cell cycle, and DNA methylation following curcumin treatment were also evaluated. We observed that curcumin inhibited the proliferation, colony formation, and migration of hGCCs in a dose- and time-dependent fashion. A high concentration of curcumin elevated ROS levels and triggered mitochondrial damage, DNA damage, and apoptosis of hGCCs. Further, curcumin-induced DNA demethylation of hGCCs was mediated by the damaged DNA repair-p53-p21/GADD45A-cyclin/CDK-Rb/E2F-DNMT1 axis. We propose that the anticancer effect of curcumin could largely be attributed to its prooxidative effect at high concentrations and ROS elevation in cancer cells. Moreover, we present a novel mechanism by which curcumin induces DNA demethylation of hGCCs, suggesting the need to further investigate the demethylation mechanisms of other DNA hypomethylating drugs.

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Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer

Cited by 14 publications

References 27 publications

LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p

LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p

Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells

Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway

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