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

Sumitaka Yamanaka, Alexandru V. Olaru, Fangmei An, Delgermaa Luvsanjav, Zhe Jin, Rachana Agarwal, Ciprian Tomuleasa, Irinel Popescu, Sorin Alexandrescu, Simona Dima, Mihaela Chivu-Economescu, Elizabeth A. Montgomery, Michael Torbenson, Stephen J. Meltzer, Florin M. Selaru

Research output: Contribution to journalArticle

Abstract

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'UTR. 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.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalDigestive and Liver Disease
Volume44
Issue number7
DOIs
StatePublished - Jul 1 2012

Keywords

  • Gastric cancer
  • MicroRNA-21
  • Serpini1 gene

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Yamanaka, S., Olaru, A. V., An, F., Luvsanjav, D., Jin, Z., Agarwal, R., Tomuleasa, C., Popescu, I., Alexandrescu, S., Dima, S., Chivu-Economescu, M., Montgomery, E. A., Torbenson, M., Meltzer, S. J., & Selaru, F. M. (2012). MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer. Digestive and Liver Disease, 44(7), 589-596. https://doi.org/10.1016/j.dld.2012.02.016