title: Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis.
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.
authors.affiliation: 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@163.com.
authors.forename: Fengchang
authors.initials: F
authors.lastname: Qiao
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Pihai
authors.initials: P
authors.lastname: Gong
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Hu
authors.forename: Sen
authors.initials: S
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015536:Down-Regulation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human