Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication

Yoshimasa Saito; Hidekazu Suzuki; Hitoshi Tsugawa; Hiroyuki Imaeda; Juntaro Matsuzaki; Kenro Hirata; Naoki Hosoe; Masahiko Nakamura; Makio Mukai; Hidetsugu Saito; Toshifumi Hibi

doi:10.1371/journal.pone.0047396

Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication

PLoS One. 2012;7(11):e47396. doi: 10.1371/journal.pone.0047396. Epub 2012 Nov 28.

Authors

Yoshimasa Saito¹, Hidekazu Suzuki, Hitoshi Tsugawa, Hiroyuki Imaeda, Juntaro Matsuzaki, Kenro Hirata, Naoki Hosoe, Masahiko Nakamura, Makio Mukai, Hidetsugu Saito, Toshifumi Hibi

Affiliation

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinjuku-ku, Tokyo, Japan.

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

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Animals
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Base Sequence
Biomarkers, Tumor
C-Reactive Protein / genetics
Disease Models, Animal
Female
Gastric Mucosa / metabolism
Gastric Mucosa / microbiology
Gastric Mucosa / pathology
Gene Expression
Gene Expression Regulation, Neoplastic
Helicobacter Infections / drug therapy
Helicobacter heilmannii / drug effects
Humans
Lymphoma, B-Cell, Marginal Zone / genetics*
Male
Mice
MicroRNAs / chemistry
MicroRNAs / genetics*
Middle Aged
Molecular Sequence Data
Nerve Tissue Proteins / genetics
Oncogene Proteins, Fusion / genetics
Stomach Neoplasms / genetics*
Translocation, Genetic
Tumor Suppressor Protein p53 / genetics

Substances

API2-MALT1 fusion protein, human
Anti-Bacterial Agents
Biomarkers, Tumor
MIRN142 microRNA, human
MIRN155 microRNA, human
MicroRNAs
Nerve Tissue Proteins
Oncogene Proteins, Fusion
Tumor Suppressor Protein p53
neuronal pentraxin
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.