Deregulation of miRNA in Helicobacter pylori-Induced Gastric MALT Lymphoma: From Mice to Human

Abstract

Gastric MALT lymphoma (GML) is directly caused by Helicobacter pylori infection but occurs only in a small number of infected subjects. Mechanisms underlying the initiation and progression of GML remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that are now considered as major players in inflammation and carcinogenesis, acting as oncogenes or tumor suppressors. Previous laboratory studies have shown in a GML mouse model that overexpression of a distinct set of five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) could play a critical role in the pathogenesis of GML. Our goal was to compare the miRNA expression profile obtained in the GML mouse model to that in human GML (11 cases of GML compared to 17 cases of gastritis control population). RTqPCR on the five dysregulated miRNAs in the GML mouse model and PCR array followed by RTqPCR confirmation showed that four miRNAs were up-regulated (miR-150, miR-155, miR-196a, miR-138) and two miRNAs down-regulated (miR-153, miR-7) in the stomachs of GML patients vs. gastritis control population. The analysis of their validated targets allowed us to postulate that these miRNAs (except miR-138) could act synergistically in a common signaling cascade promoting lymphomagenesis and could be involved in the pathogenesis of GML.

Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

“…Recently, Blosse et al showed that four novel miRNAs (miR-150, miR-155, miR-196a, and miR-138) played important regulatory roles in the pathogenesis of gastric MALT lymphoma caused by Helicobacter pylori infection [50]. Consistent with the results reported for gastric MALT lymphoma, we found that miR-138 was expressed at higher levels in biopsy tissues of orbital MALT lymphoma patients compared with IgG4-ROD.…”

Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID

“…NF-kB and MYB directly activate the expression of miR-155 in B cells, provoking the unblocking of AKT activity and influencing BCR signaling. NF-kB and BCR activation plays a key role in MALT lymphomagenesis [ 23 ]. Former studies have shown the upregulation of miR-142 and miR-155 when comparing human GML tissue to normal mucosa [ 24 ] and chronic gastritis [ 25 ].…”

“…Former studies have shown the upregulation of miR-142 and miR-155 when comparing human GML tissue to normal mucosa [ 24 ] and chronic gastritis [ 25 ]. Both miR-142 and miR-155 inhibit the pro-apoptoticstress-induced P53 target gene (TP53INP1), thus accelerating MALT lymphoma proliferation [ 23 ]. Fernandez et al proposed the use of the quantitative expression of miR-142-3p and miR-155 to better distinguish between chronic gastritis and gastric MALT lymphoma.…”

“…Additionally, lymphangiogenesisis regulated by miR-155 in the human NKTCL cell line [ 28 ]. Moreover, a worst response to HP eradication therapy in MALT lymphoma is related to the upregulation of miR-155 [ 23 ]. In contrast, in metastatic GML, both of these miRNAs have been found to be downregulated [ 25 ].…”

Proteomic and transcriptomic studies of BGC823 cells stimulated with Helicobacter pylori isolates from gastric MALT lymphoma

“…pylori -induced gastric lymphomagenesis in a mouse model and compared the miRNA expression profile obtained in the GML mouse model to that in human. They revealed the upregulation of a series of chemokine ligand, interleukin, tumor necrosis factor, miR-150, miR-155, miR-196a and miR-138 could be involved in the pathogenesis of GML [ 40 , 41 ]. Consistent with this, in this study, by transcriptomic analysis, we found some miRNA and chemokine ligand may take roles in the pathogenesis of GML.…”