Functional Role of RRS1 in the Chemosensitivity of Drug Resistant Breast Cancer Cell to Cisplatin

RRS1(human regulator of ribosome synthesis 1), a critical nuclear protein participated in ribosome biogenesis, plays important roles in the genesis and development of breast cancer. Here, we reported that RRS1 was highly expressed in cisplatin resistant breast cancer cell MCF-7/DDP than that in parent MCF-7. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin, inhibited proliferation, affected cell cycle distribution and promoted apoptosis. Furthermore, in nude mice xenograft study, the content of RRS1 in cisplatin treatment group was significantly higher than that in saline treatment group. In addition, we found that RRS1 could bind to AEG-1 and subsequently strengthened AEG-1 abundance in breast cancer cells. Although AEG-1 did not affect AEG-1 gene transcription, it inhibited ubiquitination and subsequent proteasome-mediated degradation of AEG-1 protein. Our research in current study documented for the first time that RRS1 participated in the sensitivity of breast cancer cells to cisplatin through binding to AEG-1, indicating that RRS1 may be a promising target for the therapy of breast cancer.