Inhibition of Proliferation by Knockdown of Transmembrane (TMEM) 168 in Glioblastoma Cells via Suppression of Wnt/β-Catenin Pathway

Abstract

Human glioblastoma multiforme (GBM) accounts for the majority of human brain gliomas. Several TMEM proteins, such as TMEM 45A, TMEM 97, and TMEM 140, are implicated in human brain gliomas. However, the roles of TMEM168 in human GBM remain poorly understood. Herein we found that mRNA levels of TMEM168 were overexpressed in GBM patients ( n = 85) when compared with healthy people ( n = 10), which was also supported by data from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis of Gene Expression Omnibus dataset GSE16011 suggested that enhanced TMEM168 expression was associated with shorter survival time. To investigate whether and how TMEM168 functioned in the tumorigenesis of human GBM cells, two human GBM cell lines (U87 and U373) were used for study. Lithium chloride (LiCl), an activator for Wnt/β-catenin pathway, was used for the treatment. Our data suggested that siRNA-TMEM168 (siTMEM168) prevented viability of U87 and U373 cells, induced cell cycle arrest (G 0 /G 1 phase) and promoted apoptosis, and the mechanisms involved in blocking Wnt/β-catenin pathway, as evidenced by reducing expression of β-catenin, C-myc, cyclin D1, and survivin. Furthermore, the inhibited effect of siTMEM168 on human GBM cell growth was significantly alleviated with additional LiCl treatment, substantiating the involvement of the Wnt/β-catenin pathway in this process. In summary, our data demonstrated that TMEM168 may represent a therapeutic target for the treatment of human GBM.

Integrated in-depth bioinformatic analysis suggests RELCH/KIAA1468, LINC02341, and AKAP11 as candidate genes for ages at menarche and menopause

“…The lack of the GO Ontology data about RELCH/KIAA1468, PIGN, and LINC02341 may suggest that their role in metabolic pathways is still poorly studied. On the other hand, there is extensive evidence about coexpression of RELCH/KIAA1468 and PIGN with many genes, including those involved in the control of the basic cellular processes, e.g., cell proliferation [36] (Supplementary Table 4).…”

Downregulation of TMEM220 Promotes Tumor Progression in Hepatocellular Carcinoma

“…Mechanism studies showed that overexpression of TMEM220 could regulate β-catenin and FOXO3 transcriptional activity by altering their subcellular localization, affecting the expression of downstream gene p21 and SNAIL, and ultimately reducing the progression of HCC.Conclusion: Altogether, our study proposes a working model in which upregulation of TMEM220 expression alters the genes expression involved in cell proliferation, thereby inhibiting HCC progression, which suggests that TMEM220 might serve as a clinical biomarker.Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

“…Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma

“…Mechanism studies showed that overexpression of TMEM220 could regulate β-catenin and FOXO3 transcriptional activity by altering their subcellular localization, affecting the expression of downstream gene p21 and SNAIL, and ultimately reducing the progression of HCC.Conclusion: Altogether, our study proposes a working model in which upregulation of TMEM220 expression alters the genes expression involved in cell proliferation, thereby inhibiting HCC progression, which suggests that TMEM220 might serve as a clinical biomarker.Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”

“…Transmembrane protein 220 (TMEM220) is a family member of TMEMs that spans the entire width of the lipid bilayer and is permanently anchored. Many TMEMs from mammalian cells are well characterized in term of biological functions and structures [15][16][17][18], like G protein-coupled receptors (GPCR) [19][20][21], while the subcellular localization, physiological function and its role in cancer of TMEM220 remain blank. Recent studies reported LncRNAs TMEM220 is associated with HCC patients survival, and TMEM220 gene expression is downregulated in gastric cancer [22,23].…”