Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer
Metrics: PDF 1644 views | HTML 2509 views | ?
Yu Fujita1,2, Shigehiro Yagishita3, Fumitaka Takeshita1, Yusuke Yamamoto1, Kazuyoshi Kuwano2, Takahiro Ochiya1
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan
3Depertment of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Takahiro Ochiya, e-mail: [email protected]
Keywords: RPN2, NSCLC, RNAi, siRNA, malignancy
Received: October 02, 2014 Accepted: November 20, 2014 Published: December 17, 2014
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.