Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma

Kang,Wei; Tong,Joanna H.M.; Chan,Anthony W.H.; Zhao,Junhong; Wang,Shiyan; Dong,Yujuan; Sin,Frankie M.C.; Yeung,Saifung; Cheng,Alfred S.L.; Yu,Jun; To,Kafai

doi:10.3892/or.2014.3148

Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma

Authors:
- Wei Kang
- Joanna H.M. Tong
- Anthony W.H. Chan
- Junhong Zhao
- Shiyan Wang
- Yujuan Dong
- Frankie M.C. Sin
- Saifung Yeung
- Alfred S.L. Cheng
- Jun Yu
- Kafai To
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Affiliations: Department 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, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
Published online on: April 23, 2014 https://doi.org/10.3892/or.2014.3148
Pages: 2579-2586

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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.

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