Abstract
Emerging studies have indicated that microRNAs are involved in the development and progression of cancer. Here we found that miR-202-3p was frequently down-regulated in gastric cancer tissues. Overexpression of miR-202-3p in gastric cancer cells MKN-28 and BGC-823, markedly suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, Gli1 expression was frequently positive in gastric cancer tissues and inversely correlated with miR-133b expression. We demonstrate that the transcriptional factor Gli1 was a target of miR-202-3p and plays an essential role as a mediator of the biological effects of miR-202-3p in gastric cancer. MiR-202-3p also inhibited the expression of γ-catenin and BCL-2. Taken together, these findings suggest that miR-202-3p may function as a novel tumor suppressor in gastric cancer and its anti-tumor activity may attribute the direct targeting and inhibition of Gli1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Animals
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Apoptosis
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Carcinoma / genetics*
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Carcinoma / metabolism
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Carcinoma / pathology
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Carcinoma / surgery
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Cell Line, Tumor
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Female
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Gastrectomy
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Gene Expression Regulation, Neoplastic*
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Genetic Vectors
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Humans
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Male
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Mice
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Mice, Nude
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Middle Aged
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Retroviridae / genetics
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Stomach Neoplasms / genetics*
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology
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Stomach Neoplasms / surgery
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Tumor Burden
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Zinc Finger Protein GLI1
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gamma Catenin / antagonists & inhibitors
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gamma Catenin / genetics
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gamma Catenin / metabolism
Substances
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GLI1 protein, human
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MIRN133 microRNA, human
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MIRN202 microRNA, human
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MicroRNAs
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Proto-Oncogene Proteins c-bcl-2
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Transcription Factors
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Zinc Finger Protein GLI1
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gamma Catenin
Grants and funding
This study was supported by Grants from National Natural Science Foundation of China (Nos. 81072012, 81101847, 81172324, 91229106 and 81272749), Science and Technology Commission of Shanghai Municipality (Nos. 10jc1411100, 11jc1407602, 09DZ1950100, 09DZ2260200, 12XD1403700 and 12PJ1406300), Key Projects in the National Science and Technology Pillar Program of China (No. 2011BA203191), Research Fund for the Doctoral Program of Higher Education of China (No. 20110073110071), Key Project of Shanghai Education Committee (Nos. 12ZZ102, 12ZZ105) and Innovation Foundation for PhD Graduates of Shanghai Jiao Tong University School of Medicine (BXJ201213). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.