A regulator of ribosome synthesis 1 (RRS1) was discovered in yeast and is mainly localized in the nucleolus and endoplasmic reticulum. It regulates ribosomal protein, RNA biosynthesis, and protein secretion and is closely involved in cellular senescence, cell cycle regulation, transcription, translation, oncogenic transformation etc., Mutations in the RRS1 gene are associated with the occurrence and development of Huntington’s disease and cancer, and overexpression of RRS1 promotes tumor growth and metastasis. In this review, the structure, function, and mechanisms of RRS1 in various diseases are discussed.

Regulator of ribosome synthesis 1 (RRS1) is a key factor in ribosome biosynthesis and other cellular functions. High level of RRS1 in breast cancer cell lines is associated with increased cell proliferation, invasion and migration. RRS1 controls the assembly of the 60s subunit and maturation of 25S rRNA during ribosome biosynthesis. In this study, lentiviral transfection of sh-RNA was used to knock down the level of RRS1, to detect the effect of RRS1 on cell function and to explore the specific mechanism of RRS1 affecting cell invasion and metastasis by COIP and dual-luciferase reporter gene assays. The present study found that RRS1 knockdown reduced the accumulation of ribosome protein L11 (RPL11) in the nucleolus, which then migrated to the nucleoplasm and bound to c-Myc. This inhibited trans-activation of SNAIL by c-Myc and eventually decreased the invasion and metastasis capacity of the human breast cancer cell line BT549. Taken together, RRS1 regulates invasion and metastasis of human breast cancer cells through the RPL11-c-Myc-SNAIL axis. The findings are of great significance for exploring the mechanism of breast cancer invasion and metastasis and the corresponding regulatory factors.

Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein involved in ribosome biogenesis, also plays a key role in the genesis and development of breast cancer by protecting cancer cells from apoptosis. Given that apoptosis resistance is one of the causes of the cisplatin resistance of tumor cells, our aim was to determine the relationship between RRS1 and cisplatin resistance in breast cancer cells. Here, we report that RRS1 is associated with cisplatin resistance in breast cancer cells. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin and inhibited cancer cell proliferation by blocking cell cycle distribution and enhancing apoptosis. AEG-1 (astrocyte elevated gene-1) promotes drug resistance by interfering with the ubiquitination and proteasomal degradation of MDR1 (multidrug resistance gene 1), thereby enhancing drug efflux. We found that RRS1 binds to and stabilizes AEG-1 by inhibiting ubiquitination and subsequent proteasomal degradation, which then promotes drug efflux by upregulating MDR1. Furthermore, RRS1 also induces apoptosis resistance in breast cancer cells through the ERK/Bcl-2/BAX signaling pathway. Our study is the first to show that RRS1 sensitizes breast cancer cells to cisplatin by binding to AEG-1, and it provides a theoretical basis to improve the efficacy of cisplatin-based chemotherapy.

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.