<i>MAL</i> and <i>TMEM220</i> are novel DNA methylation markers in human gastric cancer

Choi, Boram; Han, Tae Su; Min, Jimin; Hur, Keun; Lee, Sun Min; Lee, Hyuk Joon; Kim, Young-Joon; Yang, Han Kwang

doi:10.1080/1354750x.2016.1201542

Cited by 27 publications

(21 citation statements)

References 44 publications

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“…On the other hand, down-regulation of MAL alone 34 and both MAL and BENE was confirmed in cervical squamous cancer 35, similar to the loss of MAL expression in dysplastic esophageal lesions in humans and rats 36. MAL -promoter hypermethylation and concomitant MAL -down-regulation have been described in other epithelial malignancies such colon cancer 37,38, breast cancer 39,40, stomach cancer 41,42, salivary gland cancer 43, other head and neck carcinomas 44,45, non-small cell lung cancer (NSCLC) 46, and bladder cancer 47. In mammals, cytosine methylation occurs in highly repeated CpG dinucleotide regions called CpG islands, which are located in promoters and intragenic regions of many genes, mainly cell cycle regulators and tumor suppressors 48,49.…”

Section: The Two Roles Of Mal In Cancermentioning

confidence: 62%

On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Lara-Lemus¹

2019

J. Cancer

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Myelin and lymphocyte protein (MAL) is an integral membrane protein constituent of lipid rafts, and it is implicated in apical transport of proteins in polarized epithelial cells. However, beyond the involvement of MAL in apical sorting and as its function as a raft stabilizer, it is still not totally clear how MAL participates in cell proliferating processes. More controversial and interesting is the fact that MAL has been implicated in carcinogenesis in two opposite ways. First, this protein is overexpressed in ovarian cancer and some kinds of lymphomas where it seems to favor cancer progression. Conversely, it has been reported that downregulation of the MAL gene by promoter hypermethylation is a hallmark of several adenocarcinomas. So far, there is not enough experimental evidence to help us understand this phenomenon, and no MAL mutations or MAL isoforms have been associated with these opposite functions. This review provides an updated summary of the structure and functions of MAL, and we will discuss the possible mechanisms underlying its roles as a tumor suppressor and a tumor progression factor.

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Section: The Two Roles Of Mal In Cancermentioning

confidence: 62%

On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Lara-Lemus¹

2019

J. Cancer

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“…Recently, a study find that TMEM220 was down-regulated and highly methylated in GC tissues compared to normal tissues. The demethylation experiment also implied that the methylation of TMEM220 was inversely correlated with its expression (Choi et al, 2017). Therefore, we suggest that CTC-297N7.9 may be able to regulate the methylation of TMEM220 , or be involved in cell autophagy through the interaction with functional proteins, and then affect the prognosis of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of four prognostic LncRNAs for survival prediction of patients with hepatocellular carcinoma

Wang

Feng

et al. 2017

PeerJ

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BackgroundAs the fifth most common cancer worldwide, Hepatocellular carcinoma (HCC) is also the third most common cause of cancer-related death in China. Several lncRNAs have been demonstrated to be associated with occurrence and prognosis of HCC. However, identification of prognostic lncRNA signature for HCC with expression profiling data has not been conducted yet.MethodsWith the reuse of public available TCGA data, expression profiles of lncRNA for 371 patients with HCC were obtained and analyzed to find the independent prognostic lncRNA. Based on the expression of lncRNA, we developed a risk score model, which was evaluated by survival analysis and ROC (receiver operating characteristic) curve. Enrichment analysis was performed to predict the possible role of the identified lncRNA in HCC prognosis.ResultsFour lncRNAs (RP11-322E11.5, RP11-150O12.3, AC093609.1, CTC-297N7.9) were found to be significantly and independently associated with survival of HCC patients. We used these four lncRNAs to construct a risk score model, which exhibited a strong ability to distinguish patients with significantly different prognosis (HR = 2.718, 95% CI [2.103–3.514], p = 2.32e−14). Similar results were observed in the subsequent stratification survival analysis for HBV infection status and pathological stage. The ROC curve also implied our risk score as a good indicator for 5-year survival prediction. Furthermore, enrichment analysis revealed that the four signature lncRNAs may be involved in multiple pathways related to tumorigenesis and prognosis.DiscussionOur study recognized four lncRNAs to be significantly associated with prognosis of liver cancer, and could provide novel insights into the potential mechanisms of HCC progression. Additionally, CTC-297N7.9 may influence the downstream TMEM220 gene expression through cis-regualtion. Nevertheless, further well-designed experimental studies are needed to validate our findings.

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“…DNA methylation is acknowledged as the principle mechanism of dysfunction of tumor suppressor genes [ 7 ] and the activation of oncogenes [ 8 ]. DNA methylation has been widely studied in GC and CRC [ 9 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

The role of TFPI2 hypermethylation in the detection of gastric and colorectal cancer

Chen

Wang

et al. 2017

Oncotarget

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Gastrointestinal cancer is a prevalent disease with high morbidity and mortality. Tissue factor pathway inhibitor 2 (TFPI2) gene could protect the extracellular matrix of cancer cells from degradation and tumor invasion. The goal of our study was to estimate the diagnostic value of TFPI2 hypermethylation in gastric cancer (GC) and colorectal cancer (CRC). TFPI2 methylation was measured by quantitative methylation-specific polymerase chain reaction (qMSP) method in 114 GC and 80 CRC tissues and their paired non-tumor tissues. Our results showed that TFPI2 methylation was significantly higher in tumor tissues (GC: 29.940% vs. 12.785%, P < 0.001; CRC: 26.930% vs. 5.420%, P < 0.001). The methylation level of TFPI2 in colorectal tumor tissues was significantly higher than that in colorectal normal tissues (26.930% versus 0.002%, P < 0.00001). In GC, TFPI2 hypermethylation yielded an area under the curve (AUC) of 0.762 (95% CI: 0.696–0.828) with a sensitivity of 68% and a specificity of 83%. In CRC, TFPI2 hypermethylation yielded an AUC of 0.759 (95% CI: 0.685–0.834) with a sensitivity of 61% and a specificity of 84%. Similarly, TCGA data also supported TFPI2 hypermethylation was a promising diagnostic marker for GC and CRC. Moreover, the dual-luciferase reporter assay showed TFPI2 fragment could upregulate gene expression (fold change = 5, P = 0.005). Data mining further indicated that TFPI2 expression in CRC cell lines was significantly increased after 5’-AZA-deoxycytidine treatment (fold change > 1.37). In conclusion, TFPI2 hypermethylation might be a promising diagnostic biomarker for GC and CRC.

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MAL and TMEM220 are novel DNA methylation markers in human gastric cancer

Abstract: These loci may serve as novel methylation markers for patients with GC.

Cited by 27 publications

References 44 publications

On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Identification of four prognostic LncRNAs for survival prediction of patients with hepatocellular carcinoma

The role of TFPI2 hypermethylation in the detection of gastric and colorectal cancer

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