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Published on: August 18, 2010
Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric
Wei Kang1, Joanna H M Tong1, Anthony W H Chan1
1Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China.
Abstract:
Ribonucleotide reductase M2 subunit (RRM2) is one of the two subunits of human ribonucleotide reductase which plays a critical role in tumor progression. The aim of the present study was to analyze its expression, clinical significance and biological functions in gastric adenocarcinoma. We observed the upregulation of RRM2 mRNA and protein in all nine gastric cancer cell lines examined. In paired primary gastric cancers, both mRNA and protein levels of RRM2 were significantly upregulated in tumors compared with the corresponding non-tumorous gastric tissues. RRM2 protein expression correlated with higher tumor grade, advanced T stage and poor disease-specific survival. RRM2 knockdown in gastric cancer cell lines AGS, MKN1 and MKN28 significantly suppressed cell proliferation, inhibited monolayer colony formation, reduced cell invasion and induced apoptosis. Downregulation of RRM2 suppressed xenograft formation in vivo. Collectively, these findings suggest that RRM2 plays a crucial role in gastric tumorigenesis and may serve as a potential prognostic marker and therapeutic target in gastric cancer.
Insights
Ribonucleotide reductase M2 subunit (RRM2) is upregulated in gastric cancer, correlating with poor prognosis. Inhibiting RRM2 suppressed tumor growth, invasion, and promoted apoptosis, indicating its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ribonucleotide reductase M2 subunit (RRM2) is essential for DNA synthesis and is implicated in tumor progression.
- Its role in gastric adenocarcinoma requires further investigation for potential therapeutic applications.
Purpose of the Study:
- To investigate the expression, clinical significance, and biological functions of RRM2 in gastric adenocarcinoma.
- To evaluate RRM2 as a prognostic marker and therapeutic target in gastric cancer.
Main Methods:
- Analysis of RRM2 mRNA and protein expression in gastric cancer cell lines and paired tumor/non-tumor tissues.
- Correlation analysis of RRM2 expression with clinical parameters (tumor grade, T stage, survival).
- In vitro (cell lines) and in vivo (xenograft) studies to assess the functional impact of RRM2 knockdown.
Main Results:
- RRM2 was significantly upregulated in gastric cancer cell lines and primary tumors compared to non-tumorous tissues.
- RRM2 expression correlated with higher tumor grade, advanced T stage, and poorer disease-specific survival.
- RRM2 knockdown suppressed gastric cancer cell proliferation, colony formation, invasion, induced apoptosis, and inhibited xenograft tumor growth.
Conclusions:
- RRM2 plays a critical role in gastric tumorigenesis.
- RRM2 serves as a potential prognostic biomarker for gastric cancer.
- RRM2 represents a promising therapeutic target for gastric cancer treatment.
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