NGALR Is Overexpressed and Regulated by Hypomethylation in Esophageal Squamous Cell Carcinoma

Abstract

The identification of surface proteins on the plasma membrane of pathogens is of fundamental importance in understanding host-pathogen interactions. Surface proteins of the extracellular parasite Trichomonas are implicated in the initial adherence to mucosal tissue and are likely to play a critical role in the long term survival of this pathogen in the urogenital tract. In this study, we used cell surface biotinylation and multidimensional protein identification technology to identify the surface proteome of six strains of Trichomonas vaginalis with differing adherence capacities to vaginal epithelial cells. A combined total of 411 proteins were identified, and of these, 11 were found to be more abundant in adherent strains relative to less adherent parasites. The mRNA levels of five differentially expressed proteins selected for quantitative RT-PCR analysis mirrored their observed protein levels, confirming their up-regulation in highly adherent strains. As proof of principle and to investigate a possible role in pathogenesis for differentially expressed proteins, gain of function experiments were performed using two novel proteins that were among the most highly expressed surface proteins in adherent strains. Overexpression of either of these proteins, TVAG_244130 or TVAG_166850, in a relatively non-adherent strain increased attachment of transfected parasites to vaginal epithelial cells ϳ2.2-fold. These data support a role in adhesion for these abundant surface proteins. Our analyses demonstrate that comprehensive profiling of the cell surface proteome of different parasite strains is an effective approach to identify potential new adhesion factors as well as other surface molecules that may participate in establishing and maintaining infection by this extracellular pathogen. Molecular & Cellular Proteomics 9:1554 -1566, 2010.

Epigenetic regulation of miR‐196b expression in gastric cancer

“…A recent study indicated that treatment of cancer cells with demethylation drugs results in increased invasive and metastatic phenotypes via the restoration of the expression of certain oncogenes, such as TGFb, ROS, and MMP (Shukeir et al, 2006;Ateeq et al, 2008;Cui et al, 2008;Jun et al, 2009). A recent study indicated that miR-196a-2 might have a potentially oncogenic role in breast tumorigenesis and hypermethylation of a CpG island upstream of the miR-196a-2 precursor was also associated with reduced breast cancer risk (Hoffman et al, 2009).…”

Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma

“…described that SLC22A17 overexpression was induced by hypomethylation of the NGALR promoter (Cui et al, 2008). Sheng et al reported that SLC22A17 expression was regulated by Runx transcription factors; Runx3 activated and Runx1 repressed the expression (Sheng et al, 2009).…”

Upregulation and CpG Island Hypomethylation of the TRF2 Gene in Human Gastric Cancer

“…However, overexpression of oncogenes was postulated to be the result of DNA hypomethylation. For example, NGALR is overexpressed and regulated by hypomethylation in esophageal squamous cell carcinomas [16]. Hypomethylation of Synuclein gene CpG islands promote its aberrant expression in breast carcinoma and ovarian carcinoma.…”