Functional role of RRS1 in breast cancer cell proliferation

Abstract

RRS1 (human regulator of ribosome synthesis 1), an essential nuclear protein involved in ribosome biogenesis, is overexpressed in some human cancers, yet its role in breast cancer remains unclear. Here, we report a functional analysis of RRS1 in breast cancer and its likely mechanism. Immunohistochemistry (IHC) and RT‐qPCR analyses indicated that RRS1 was commonly overexpressed in breast cancer tissues. The copy numbers of RRS1 were higher in tumours compared with those for normal tissues. And there was a significant correlation between copy number and mRNA expression. In addition, RRS1 overexpression was significantly correlated with lymph node metastasis and poor survival. RRS1 mRNA and protein levels were also significantly increased in a panel of human breast cancer cell lines. RRS1 knockdown inhibited proliferation and induced apoptosis and cell cycle arrest in all three cell lines. Furthermore, RRS1 knockdown suppressed the tumour formation and growth of MDA‐MB‐231 cells in nude mice. Additionally, RRS1 knockdown activated p53 and p21 in MCF‐7 cells. A marked increase in the quantity of ribosome‐free RPL11 was detected by Western blot. Moreover, co‐immunoprecipitation (CoIP) experiments showed that RRS1 knockdown activated p53 by facilitating the direct contact of MDM2 and RPL11/RPL5. Taken together, our results suggest that RRS1 may contribute to breast cancer proliferation through RPL11/MDM2‐mediated p53 activation. Therefore, RRS1 may be a promising target for breast cancer therapy.

Down-regulated lncRNA SBF2-AS1 inhibits tumorigenesis and progression of breast cancer by sponging microRNA-143 and repressing RRS1

“…Similar to this outcome, Tian et al have illuminated that the knockdown of SBF2-AS1 could repress the proliferation ability of acute myeloid leukemia cells in vitro [26], and the suppressive effects of miR-143 on the proliferation of BC cells have been revealed by a previous publication [27]. Additionally, Song et al have discovered that the degradation of RRS1 has the ability to prevent the proliferation and induce apoptosis and cell cycle arrest of BC cell lines [15]. Interestingly, this result was in line with one of our essential findings that the knockdown of SBF2-AS1 could bind to miR-143 to promote cell cycle arrest and cell apoptosis in BC by repressing RRS1.…”

“…As one of the miRNAs, microRNA-143 (miR-143) has been identified as a tumor repressor [10], and it has been demonstrated that miR-143 was implicated in the progression of BC [11][12][13]. Besides, it has been demonstrated that resistance to ralstonia solanacearum 1 (RRS1) serves as a ribosome biogenesis protein in yeast and plants [14], which has also been clarified to be associated with BC [15,16].…”

Integrated Analysis of the Functions and Prognostic Values of RNA-Binding Proteins in Colorectal Cancer

“…RRS1 plays a critical role in cell proliferation, colony formation, cell apoptosis, and cell cycle distribution in human HCC cells (Wang et al, 2017). In breast cancer, both the copy number and the mRNA expression of RRS1 increased in cancer tissues compared with normal tissues, and RRS1 overexpression was significantly correlated with lymph node metastasis and poor survival (Song et al, 2018). RRP12 was crucial for the survival of osteosarcoma cell line U2OS during cytotoxic stress via the repression of p53 stability, suggesting that target RRP12 may enhance the chemotherapeutic effect in cancers (Choi et al, 2016).…”

Advances in the Relationship Between Regulator of Ribosome Synthesis 1 (RRS1) and Diseases

“…We found that the RRS1 gene is highly expressed in breast cancer cells, and its knockdown significantly reduced the proliferation rate and increased apoptosis ( Hua et al, 2019 ). RRS1 may promote proliferation of breast cancer through p53 activation via RPL11/MDM2 ( Figure 1 ) ( Song et al, 2018 ). Taken together, RRS1 is a novel oncogene of breast cancer and a promising therapeutic target.…”