RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis.
RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis.
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DOI：
10.1038/mtna.2014.35
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发表时间：
2014-09-02
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影响因子：
--
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耐药和转移是肿瘤的致命特征。我们以前证明，沉默核糖体蛋白II（RPN 2），这是N-寡糖基转移酶复合物的一部分，有效地诱导细胞凋亡，并降低耐药多西他赛在人乳腺癌细胞。在这里，我们报告了骨肉瘤中RPN 2表达的临床和功能相关性。35例骨肉瘤患者活检组织的免疫组化评价显示，RPN 2在所有标本中中度至高度表达，RPN 2 mRNA表达较高与预后不良显著相关。为了研究是否可以通过调节RPN 2的表达来降低骨肉瘤的致死表型，我们在高转移性人骨肉瘤细胞中进行了RNAi诱导的RPN 2敲低的研究。结果表明，RPN 2沉默减少细胞增殖，球体形成，细胞侵袭和体外致敏药物反应。携带RPN 2沉默的高转移性骨肉瘤异种移植物的小鼠显示出减少的肿瘤生长和肺转移，并且比携带对照肿瘤异种移植物的小鼠存活更长。综上所述，我们的数据表明，RPN 2沉默有助于调节致死性骨肉瘤表型，并可能成为基于RNAi的骨肉瘤治疗的新靶点。
Drug resistance and metastasis are lethal characteristics of tumors. We previously demonstrated that silencing of ribophorin II (RPN2), which is part of the N-oligosaccharyl transferase complex, efficiently induced apoptosis and reduced resistance to docetaxel in human breast cancer cells. Here, we report the clinical and functional correlations of RPN2 expression in osteosarcoma. Immunohistochemical evaluation of 35 osteosarcoma patient biopsies revealed that RPN2 was moderately to highly expressed in all specimens, and higher RPN2 mRNA expression was significantly correlated with poor prognosis. To investigate whether lethal phenotypes of osteosarcoma could be reduced by regulating the expression of RPN2, we conducted a study of RNAi-induced RPN2 knockdown in highly metastatic human osteosarcoma cells. The results indicated that RPN2 silencing reduced cell proliferation, sphere formation, cell invasion, and sensitized drug response in vitro. Mice bearing RPN2-silenced highly metastatic osteosarcoma xenografts showed reduced tumor growth and lung metastasis, and survived longer than mice bearing control tumor xenografts. Taken together, our data suggest that RPN2 silencing contributes to regulation of lethal osteosarcoma phenotypes and could be a novel target for RNAi-based therapeutics against osteosarcoma.
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影响因子：
2.5
作者：
Bacci, Gaetano;Rocca, Michele;Briccoli, Antonio
通讯作者：
Briccoli, Antonio
DOI：
10.1302/0301-620x.88b5.17098
发表时间：
2006-05-01
影响因子：
--
作者：
Gupta, A;Meswania, J;Blunn, G
通讯作者：
Blunn, G
影响因子：
158.5
作者：
CORTES, EP;HOLLAND, JF;GLIDEWELL, O
通讯作者：
GLIDEWELL, O
影响因子：
50.5
作者：
Grignani, G.;Palmerini, E.;Aglietta, M.
通讯作者：
Aglietta, M.
药物补偿和治疗超出进展 - 耐药性的刺激性。
DOI：
10.1038/nrclinonc.2013.158
发表时间：
2013-10
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Kuczynski EA;Sargent DJ;Grothey A;Kerbel RS
通讯作者：
Kerbel RS