Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer.
Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer.
复制标题
DOI：
10.18632/oncotarget.2793
复制
发表时间：
2015-02-20
期刊：
影响因子：
--
通讯作者：
Ochiya T
中科院分区：
文献类型：
--
作者：
Fujita Y;Yagishita S;Takeshita F;Yamamoto Y;Kuwano K;Ochiya T
RNA干扰（RNAi）是一种用于癌症治疗的强大基因沉默平台。以前，我们证明了核糖体蛋白II（RPN 2），这是N-寡糖基转移酶复合物的一部分，调节多西他赛的敏感性和乳腺癌的肿瘤致死表型。然而，RPN 2在非小细胞肺癌（NSCLC）中的分子功能和临床相关性仍然未知。在这里，我们研究了RPN 2表达的肿瘤标本，从复发性NSCLC患者切除后（n = 32和= 177），并评估RPN 2表达和各种临床特征之间的相关性。我们还研究了RPN 2是否影响体外癌症恶性程度和体内肿瘤生长和耐药性。我们的数据表明，RPN 2表达赋予NSCLC患者早期和远处复发以及较差的生存率。此外，RPN 2沉默抑制细胞增殖和侵袭力，并增加体外化疗药物的敏感性。值得注意的是，我们发现内在凋亡信号是与RPN 2敲低有关的细胞死亡机制。引人注目的是，RPN 2沉默抑制了肿瘤发生并使肿瘤对顺铂治疗敏感，这导致携带NSCLC的小鼠存活时间更长。总之，这些数据表明，RPN 2参与调节致死性癌症表型，并代表了基于RNAi的药物治疗NSCLC的有前途的新靶点。
RNA interference (RNAi) is a powerful gene-silencing platform for cancer treatment. Previously, we demonstrated that ribophorin II (RPN2), which is part of the N-oligosaccharyl transferase complex, regulates docetaxel sensitivity and tumor lethal phenotypes in breast cancer. However, the molecular functions and clinical relevance of RPN2 in non-small-cell lung cancer (NSCLC) remain unknown. Here, we examined RPN2 expression in tumor specimens from recurrent NSCLC patients after resection (n = 32 and = 177) and assessed the correlation between RPN2 expression and various clinical features. We also investigated whether RPN2 affects cancer malignancy in vitro and tumor growth and drug resistance in vivo. Our data show that RPN2 expression confers early and distant recurrence as well as poor survival in NSCLC patients. Furthermore, RPN2 silencing suppressed cell proliferation and invasiveness, and increased the sensitivity to chemotherapeutic drugs in vitro. Remarkably, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with RPN2 knockdown. Strikingly, RPN2 silencing repressed tumorigenicity and sensitized the tumors to cisplatin treatment, which led to the longer survival of NSCLC-bearing mice. In conclusion, these data suggest that RPN2 is involved in the regulation of lethal cancer phenotypes and represents a promising new target for RNAi-based medicine against NSCLC.
登录
查看更多内容
DOI：
10.1038/mtna.2014.35
发表时间：
2014-09-02
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
82.9
作者：
Honma, Kimi;Iwao-Koizumi, Kyoko;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro
影响因子：
6.4
作者：
RADFORD, KJ;MALLESCH, J;HERSEY, P
通讯作者：
HERSEY, P
影响因子：
4.4
作者：
Zhu, Jianhui;He, Jintang;Liu, Yashu;Simeone, Diane M.;Lubman, David M.
通讯作者：
Lubman, David M.
影响因子：
4.6
作者：
Takahashi, Ryou-u;Takeshita, Fumitaka;Honma, Kimi;Ono, Masaya;Kato, Kikuya;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro