Deregulation of MicroRNAs in Gastric Lymphomagenesis Induced in the d3Tx Mouse Model of Helicobacter pylori Infection

Abstract

Helicobacter pylori infection is considered as an excellent model of chronic inflammation-induced tumor development. Our project focuses on gastric MALT lymphoma (GML) related to H. pylori infection and mediated by the chronic inflammatory process initiated by the infection. Recently, microRNAs (miRNAs) have emerged as a new class of gene regulators, which play key roles in inflammation and carcinogenesis acting as oncogenes or tumor suppressors. Their precise characterization in the development of inflammation and their contribution in regulating host cells responses to infection by H. pylori have been little explored. Our goal was to analyze the changes in miRNAs in a GML mouse model using BALB/c mice thymectomized at day 3 post-birth (d3Tx model) and to clarify their implication in GML pathogenesis. PCR array followed by RT-qPCR identified five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) overexpressed in the stomachs of GML-developing d3Tx mice infected by H. pylori. The analysis of their putative targets allowed us to identify TP53INP1, an anti-proliferative and pro-apoptotic protein, as a common target of 4 of the 5 up-regulated miRNAs. We postulate that these miRNAs may act in synergy to promote the development of GML. miR-142a was also overexpressed in mouse sera samples and therefore could serve as a diagnostic marker. In situ hybridization on gastric samples with miR-142a revealed a global up-regulation of this miRNA by the tumor microenvironment at the lymphoma stage. Dysregulation of miR-21a, miR-135b, miR-142a, miR-150, miR-155 could play a critical role in the pathogenesis of GML and might offer potential applications as therapeutic targets and novel biomarkers for this disease.

Proteomics of Brucella

“…Since 2012, some of these technological advances have been implemented, yet traditional methods have remained popular in Brucella proteomics. There have been frequent uses of 2D-PAGE and MALDI-TOF (-TOF) [ 25 , 26 , 27 , 28 , 29 , 30 ], sometimes utilizing DIGE to minimize gel-to-gel variation [ 31 , 32 ] or other fluorescent dyes for extended dynamic range [ 33 ]. Additionally, the unusual combination of 2D-PAGE with LC-MS/MS has been reported [ 34 ].…”

“…Additionally, the unusual combination of 2D-PAGE with LC-MS/MS has been reported [ 34 ]. The multiplexing of samples and the MS/MS-based quantification of iTRAQ reporter ions [ 35 , 36 ], or alternatively with Isotope Coded Protein Labeling (ICPL) [ 32 ] has been pursued. In-solution digestion [ 37 , 38 , 39 , 40 , 41 ], or in-gel digestion [ 42 , 43 ], and LC-MS/MS were sometimes employed.…”

Helicobacter pylori, gastric cancer and other gastrointestinal malignancies

“…They found five miRNAs overexpressed in GML. They identified TP53INP1, an antiproliferative and pro‐apoptotic protein, as a common target of 4 of the 5 upregulated miRNAs, suggesting these miRNAs may act in synergy to promote the development of GML …”

Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren’s Syndrome through an Impaired Epigenetic Control: The State-of-The-Art

“…The expression of micro-RNAs is tissue-related and may be induced by infectious stimuli: for example, infections due to Helicobacter pylori seem to modulate the expression of some micro-RNAs controlling cell proliferation and survival. Floch et al have demonstrated in a gastric MALT lymphoma mouse model that chronic Helicobacter pylori infection may induce the overexpression of micro-RNAs 21a, 135b, 142a, 150, and 155, which prevents the transcription of the gene coding for the proapoptotic protein tumor protein P53-inducible nuclear protein 1 (TP53INP1) [52]. Some of these micro-RNAs control the production of antibodies (including autoantibodies) [53], and others may belong to viruses infecting host cells as in the case of EBV infection [54].…”