Aberrant Hypomethylation of<i>Solute Carrier Family 6 Member 12</i>Promoter Induces Metastasis of Ovarian Cancer

Sung, Hye Youn; Yang, San‐Duk; Park, Ae Kyung; Ju, Woong; Ahn, Jung Ja

doi:10.3349/ymj.2017.58.1.27

Cited by 14 publications

(14 citation statements)

References 16 publications

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“…Several new studies have suggested that hypomethytlation and increased expression of potential proto-oncogenes predict more aggressive and metastatic OC with a potentially lower survival. This has been seen for GABRP, SLC6A12, MGAT3, CT45, CA9, MUC13 and AGR2 (85)(86)(87)(88)(89)(90)(91).…”

Section: Potential Of Dna Methylation In Oc Prognosticssupporting

confidence: 53%

Methylation and ovarian cancer: Can DNA methylation be of diagnostic use? (Review)

Hentze

Høgdall

2019

mol clin onc

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Ovarian cancer is a silent killer and, due to late diagnosis and frequent chemo resistance in patients, the primary cause of fatality amongst the various types of gynecological cancer. The discovery of a specific and sensitive biomarker for ovarian cancer could improve early diagnosis, thereby saving lives. Biomarkers could also improve treatment, by predicting which patients will benefit from specific treatment strategies. DNA methylation is an epigenetic mechanism, and 'methylation imbalance' is characteristic of cancer. Previous research suggests that changes in DNA methylation can be used diagnostically, and that they may predict resistance to treatment. This paper gives an up-to-date overview of research investigating the potential of DNA methylation-based markers for diagnostics, prognostics, screening and prediction of drug resistance for ovarian cancer patients. DNA methylation cancer-biomarkers may be useful for cancer treatment, particularly since they are chemically stable and since cancer-associated changes in methylation typically precedes tumor growth. DNA methylation markers could improve diagnosis and treatment and might even be used for screening in the future. Furthermore, DNA methylation biomarkers could facilitate the development of precision medicine. However, at this point no biomarkers for ovarian cancer have a sufficient combination of sensitivity and specificity in a clinical setting. A reason for this is that most studies have focused on a single or a few methylation sites. More large screenings and genome-wide studies must be performed to increase the chance of identifying a DNA methylation marker which can identify ovarian cancer.Abbreviations: OC, ovarian cancer; FIGO, International Federation of Gynecology and Obstetrics; RMI, risk of malignancy index; MSP, methylation-specific PCR; miRNA, microRNA; MESC, methylated in embryonic stem cells; OS, overall survival; PFS, progression free survival

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Section: Potential Of Dna Methylation In Oc Prognosticssupporting

confidence: 53%

Methylation and ovarian cancer: Can DNA methylation be of diagnostic use? (Review)

Hentze

Høgdall

2019

mol clin onc

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“…Additionally, SLC6A8 has been shown to be related to aspects of the nervous system such as behavior (13), learning (14), and intelligence (15). Notably, many members of the GABA family have been confirmed to be involved in the occurrence and development of tumors (16)(17)(18). Loo et al found that SLC6A8 can promote brain-type creatine kinase-mediated colon cancer metastasis (19).…”

Section: Original Articlementioning

confidence: 99%

SLC6A8 is involved in the progression of non-small cell lung cancer through the Notch signaling pathway

2021

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Background: Solute carrier family 6 member 8 (SLC6A8) is known to be involved in the development of human tumors; however, the effect of SLC6A8 on the growth of non-small cell lung cancer (NSCLC) remains unclear. Here, we explored the role and potential action mechanism of SLC6A8 in NSCLC. Methods:We used public databases [Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA)] to explore the expression of SLC6A8 in NSCLC. Additionally, we used immunohistochemistry to detect the expression of SLC6A8 in NSCLC clinicopathological tissues (cancer and adjacent tissues) and Western blotting to detect the expression of SLC6A8 in NSCLC clinicopathological tissues, NSCLC cell lines (A549, H1299, H520, and H1975), and a normal epithelial cell line (BEAS-2B). Using overexpression and knockdown of the SLC6A8 gene, we analyzed the in vitro effects of SLC6A8 on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC and also the possible molecular mechanism with Notch signaling pathway.Results: Bioinformatic analysis demonstrated that SLC6A8 is highly expressed in NSCLC and is related to poor prognosis. We found that the expression of the SLC6A8 protein in human lung cancer tissues was significantly higher than that in adjacent tissues. In addition, it was also significantly higher in lung cancer cell lines (A549, H1299, H520, and H1975) than that in normal lung epithelium-BEAS-2B. Moreover, SLC6A8 overexpression promotes the proliferation, migration and invasion in vitro in NSCLC, accompanied by the activation of notch signaling pathway and the up-regulation of MMP9 and E-cadherin proteins.Knocking down SLC6A8 can inhibit the above effects on cells.Conclusions: SLC6A8 promotes the malignant progression of NSCLC and activates the Notch signaling pathway. Therefore, SLC6A8 is expected to become a molecular target for NSCLC treatment.

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“…The expression levels of ITGA10 , a biomarker of type II diabetes mellitus ( Wang et al, 2021 ), are associated with metastasis in skin cutaneous melanoma ( Nurzat et al, 2021 ). SLC6A12 is a key gene that promotes aggressive metastasis during ovarian cancer progression ( Sung et al, 2017 ). SMAD4 loss is a biomarker of squamous cell carcinoma and is used for its prognosis and prediction of treatment response ( Hernandez et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of novel biomarkers in Alzheimer’s disease based on four diagnostic models

Zou

Pan

et al. 2023

Front. Aging Neurosci.

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BackgroundDespite tremendous progress in diagnosis and prediction of Alzheimer’s disease (AD), the absence of treatments implies the need for further research. In this study, we screened AD biomarkers by comparing expression profiles of AD and control tissue samples and used various models to identify potential biomarkers. We further explored immune cells associated with these biomarkers that are involved in the brain microenvironment.MethodsBy differential expression analysis, we identified differentially expressed genes (DEGs) of four datasets (GSE125583, GSE118553, GSE5281, GSE122063), and common expression direction of genes of four datasets were considered as intersecting DEGs, which were used to perform enrichment analysis. We then screened the intersecting pathways between the pathways identified by enrichment analysis. DEGs in intersecting pathways that had an area under the curve (AUC) > 0.7 constructed random forest, least absolute shrinkage and selection operator (LASSO), logistic regression, and gradient boosting machine models. Subsequently, using receiver operating characteristic curve (ROC) and decision curve analysis (DCA) to select an optimal diagnostic model, we obtained the feature genes. Feature genes that were regulated by differentially expressed miRNAs (AUC > 0.85) were explored further. Furthermore, using single-sample GSEA to calculate infiltration of immune cells in AD patients.ResultsScreened 1855 intersecting DEGs that were involved in RAS and AMPK signaling. The LASSO model performed best among the four models. Thus, it was used as the optimal diagnostic model for ROC and DCA analyses. This obtained eight feature genes, including ATP2B3, BDNF, DVL2, ITGA10, SLC6A12, SMAD4, SST, and TPI1. SLC6A12 is regulated by miR-3176. Finally, the results of ssGSEA indicated dendritic cells and plasmacytoid dendritic cells were highly infiltrated in AD patients.ConclusionThe LASSO model is the optimal diagnostic model for identifying feature genes as potential AD biomarkers, which can supply new strategies for the treatment of patients with AD.

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Aberrant Hypomethylation ofSolute Carrier Family 6 Member 12Promoter Induces Metastasis of Ovarian Cancer

Cited by 14 publications

References 16 publications

Methylation and ovarian cancer: Can DNA methylation be of diagnostic use? (Review)

Methylation and ovarian cancer: Can DNA methylation be of diagnostic use? (Review)

SLC6A8 is involved in the progression of non-small cell lung cancer through the Notch signaling pathway

Exploration of novel biomarkers in Alzheimer’s disease based on four diagnostic models

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