Abstract
microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Animals
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Anti-Bacterial Agents / pharmacology
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Anti-Bacterial Agents / therapeutic use
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Base Sequence
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Biomarkers, Tumor
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C-Reactive Protein / genetics
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Disease Models, Animal
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Female
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Gastric Mucosa / metabolism
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Gastric Mucosa / microbiology
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Gastric Mucosa / pathology
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Gene Expression
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Gene Expression Regulation, Neoplastic
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Helicobacter Infections / drug therapy
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Helicobacter heilmannii / drug effects
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Humans
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Lymphoma, B-Cell, Marginal Zone / genetics*
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Male
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Mice
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MicroRNAs / chemistry
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MicroRNAs / genetics*
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Middle Aged
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Oncogene Proteins, Fusion / genetics
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Stomach Neoplasms / genetics*
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Translocation, Genetic
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Tumor Suppressor Protein p53 / genetics
Substances
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API2-MALT1 fusion protein, human
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Anti-Bacterial Agents
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Biomarkers, Tumor
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MIRN142 microRNA, human
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MIRN155 microRNA, human
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MicroRNAs
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Nerve Tissue Proteins
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Oncogene Proteins, Fusion
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Tumor Suppressor Protein p53
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neuronal pentraxin
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C-Reactive Protein
Grants and funding
This work was supported by Grant-in-Aid for Young Scientists A (23680090 to Y.S.) and Grant-in-Aid for Scientific Research B (22300169 to H.S.) from Japan Society for Promotion of Science (
www.jsps.go.jp), Takeda Science Foundation (
www.takeda-sci.or.jp; to Y.S.), Sagawa Foundation for Promotion of Cancer Research (sagawa-gan.or.jp; to Y.S.), Smoking Research Foundation (
www.srf.or.jp; to H.S.), and Keio Gijuku Academic Development Funds (
www.keio.ac.jp; to Y.S. and H.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.