Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma
Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma
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小干扰RNA靶向核糖核苷酸还原酶M2亚基在胃腺癌中发挥抗癌作用
DOI：
10.3892/or.2014.3148
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发表时间：
2014-06-01
期刊：
影响因子：
4.2
通讯作者：
To, Kafai
中科院分区：
文献类型：
--
作者：
Kang, Wei;Tong, Joanna H. M.;To, Kafai
核糖核苷酸还原酶M2亚基（RRM2）是人类核糖核苷酸还原酶的两个亚基之一，在肿瘤进展中发挥关键作用。本研究旨在探讨其在胃腺癌组织中的表达、临床意义及生物学功能。我们观察到RRM2 mRNA和蛋白在所有9个胃癌细胞系中的上调。在配对的原发性胃癌中，与相应的非肿瘤胃组织相比，RRM2的mRNA和蛋白水平在肿瘤中均显著上调。RRM2蛋白表达与高肿瘤分级、晚期T分期和低疾病特异性生存率相关。在胃癌细胞系AGS、MKN 1和MKN 28中，RRM2的敲低显著抑制细胞增殖，抑制单层集落形成，减少细胞侵袭并诱导凋亡。RRM2的下调抑制体内异种移植物形成。总之，这些发现表明RRM2在胃肿瘤发生中起着至关重要的作用，并可能作为胃癌的潜在预后标志物和治疗靶点。
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.