Functional role of RRS1 in breast cancer cell proliferation.

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.
Mesh Terms:
Animals, Apoptosis, Breast Neoplasms, Cell Cycle Checkpoints, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, MCF-7 Cells, Mice, Nuclear Proteins, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53
J. Cell. Mol. Med.
Date: Dec. 01, 2017
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