Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma.
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.
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.
Wei
W
Kang
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.
Joanna H M
JH
Tong
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.
Anthony W H
AW
Chan
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.
Junhong
J
Zhao
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.
Shiyan
S
Wang
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.
Yujuan
Y
Dong
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.
Frankie M C
FM
Sin
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.
Saifung
S
Yeung
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China.
Alfred S L
AS
Cheng
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.
Jun
J
Yu
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.
Kafai
K
To
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics*; D012262:Ribonucleoside Diphosphate Reductase / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase