MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer

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• 作者：Sumitaka Yamanaka^a ; Alexandru V. Olaru^a ; Fangmei An^a ; Delgermaa Luvsanjav^a ; Zhe Jin^a ; Rachana Agarwal^a ; Ciprian Tomuleasa^a ; ^b ; Irinel Popescu^c ; Sorin Alexandrescu^c ; Simona Dima^c ; Mihaela Chivu-Economescu^d ; Elizabeth A. Montgomery^e ; Michael Torbenson^e ; Stephen J. Meltzer^a ; Florin M. Selaru^a ; ^{fselaru1@jhmi.edu}
• 关键词：Gastric cancer ; MicroRNA-21 ; Serpini1 gene
• 刊名：Digestive and Liver Disease
• 出版年：2012
• 期刊代码：79_15908658
• 类别：med
• 出版时间：July, 2012
• 卷：44
• 期：7
• 页码：589-596
• 文件大小：1113 K

摘要

Background

A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer.

Methods

We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay.

Results

This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3鈥睻TR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach.

Conclusion

Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.