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Updated: May 13, 2026

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2
Mitsuhiro Matsuo1, Chisato Nakada, Yoshiyuki Tsukamoto
1Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
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.
Insights
MicroRNA-29c (miR-29c) acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation. Its downregulation in gastric carcinoma is linked to increased expression of RCC2, promoting tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-29c (miR-29c) is downregulated in advanced gastric carcinoma.
- This study investigates the tumor-suppressive role of miR-29c in gastric cancer cells.
Purpose of the Study:
- To verify miR-29c downregulation in gastric carcinoma tissues.
- To assess the biological effects of miR-29c on gastric carcinoma cell behavior.
- To elucidate the molecular mechanisms underlying miR-29c's function.
Main Methods:
- MiRNA microarray analysis to identify differentially expressed genes.
- Cell transfection with miR-29c mimics and siRNAs.
- Assessment of cell proliferation, colony formation, apoptosis, and BrdU incorporation.
- Validation of target genes (RCC2, PPIC, CDK6) using 3'-UTR luciferase assays and Western blotting.
Main Results:
- Overexpression of miR-29c significantly reduced gastric cancer cell proliferation and colony formation.
- miR-29c downregulation was confirmed in gastric carcinoma tissues.
- RCC2 and PPIC were identified as direct targets of miR-29c, with RCC2 upregulation in tumors.
- Knockdown of RCC2 mimicked the anti-proliferative effects of miR-29c, suggesting its role in miR-29c-mediated growth suppression.
Conclusions:
- miR-29c exhibits tumor-suppressive functions in gastric carcinoma.
- Downregulation of miR-29c contributes to gastric tumor growth by upregulating RCC2.
- miR-29c represents a potential therapeutic target for gastric cancer.
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