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Open Access Research

MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2

Mitsuhiro Matsuo1, Chisato Nakada1, Yoshiyuki Tsukamoto1*, Tsuyoshi Noguchi2, Tomohisa Uchida1, Naoki Hijiya1, Keiko Matsuura1 and Masatsugu Moriyama1

  • * Corresponding author: Yoshiyuki Tsukamoto tuka@oita-u.ac.jp

  • † Equal contributors

Author Affiliations

1 Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan

2 Center for Community Medicine, Division of Surgery, Faculty of Medicine, Oita University, Oita, Japan

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Molecular Cancer 2013, 12:15  doi:10.1186/1476-4598-12-15

Published: 25 February 2013

Abstract

Background

Previously, using miRNA microarray, we have found that miR-29c is significantly downregulated in advanced gastric carcinoma. In the present study, we investigated whether miR-29c functions as a tumor-suppressor miRNA in gastric carcinoma cells. For this purpose, we verified the downregulation of miR-29c in gastric carcinoma tissues, and assessed the biological effect of miR-29c on gastric carcinoma cells.

Results

In miR-29c-transfected cells, both proliferation and colony formation ability on soft agar were significantly decreased. Although apoptosis was not induced, BrdU incorporation and the proportion of cells positive for phospho-histone H3 (S10) were significantly decreased in miR-29c-transfected cells, indicating that miR-29c may be involved in the regulation of cell proliferation. To explain the mechanism of growth suppression by miR-29c, we explored differentially expressed genes (>2-fold) in miR-29c-transfected cells in comparison with negative control transfected cells using microarray. RCC2, PPIC and CDK6 were commonly downregulated in miR-29c-transfected MKN45, MKN7 and MKN74 cells, and all of the genes harbored miR-29c target sequences in the 3’-UTR of their mRNA. RCC2 and PPIC were actually upregulated in gastric carcinoma tissues, and therefore both were identified as possible targets of miR-29c in gastric carcinoma. To ascertain whether downregulation of RCC2 and/or PPIC is involved in the growth suppression by miR-29c, we transfected siRNAs against RCC2 and PPIC into MKN45 and determined cell viability, the rate of BrdU incorporation, and caspase activity. We found that RCC2-knockdown decreased both cell viability and BrdU incorporation without any increase of caspase activity, while PPIC-knockdown did not, indicating that downregulation of RCC2 may be at least partly responsible for the growth suppression by miR-29c.

Conclusions

Our findings indicate that miR-29c may have tumor-suppressive functions in gastric carcinoma cells, and that its decreased expression may confer a growth advantage on tumor cells via aberrant expression of RCC2.

Keywords:
Gastric carcinoma; miR-29c; RCC2