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Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

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Abstract

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.

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Abbreviations

qRT-PCR:

Quantitative reverse-transcription polymerase chain reaction

DNMT1:

DNA methyltransferase 1

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Acknowledgments

This work was supported by the National Natural Science Foundation of China, No. 81171915 and 91229107, and the Fundamental Research Funds for the Central Universities (CXLX12_0074).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Department of Genetics and Developmental Biology, The Medical School of Southeast University and the Institute of Life Science, Southeast University, Nanjing, 210009, China

    Fengchang Qiao, Pihai Gong, Ling Wang, Jiaojiao Hu & Hong Fan

  2. The 3rd Affiliated Hospital of Harbin Medical University (Harbin Medical University Cancer Hospital), Harbin, 150081, China

    Kun Zhang

  3. The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China

    Sen Lu

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  1. Fengchang Qiao
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Correspondence to Hong Fan.

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Fengchang Qiao and Kun Zhang have equal contribution to this manuscript.

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Qiao, F., Zhang, K., Gong, P. et al. Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis. Mol Biol Rep 41, 5693–5700 (2014). https://doi.org/10.1007/s11033-014-3439-4

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