Functional role of RRS 1 in breast cancer cell proliferation

RRS 1 (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 RRS 1 in breast cancer and its likely mechanism. Immunohistoc...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2018-12, Vol.22 (12), p.6304-6313
Main Authors: Song, Jinlian, Ma, Zhongliang, Hua, Yanan, Xu, Junting, Li, Ning, Ju, Chuanxia, Hou, Lin
Format: Article
Language:English
Subjects:
Apoptosis
Breast cancer
Cell cycle
Cell proliferation
Copy number
Functional analysis
Gene expression
Immunohistochemistry
Immunoprecipitation
Lymph nodes
MDM2 protein
Metastases
p53 Protein
Tissues
Tumor cell lines
Tumors
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Summary:RRS 1 (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 RRS 1 in breast cancer and its likely mechanism. Immunohistochemistry ( IHC ) and RT ‐ qPCR analyses indicated that RRS 1 was commonly overexpressed in breast cancer tissues. The copy numbers of RRS 1 were higher in tumours compared with those for normal tissues. And there was a significant correlation between copy number and mRNA expression. In addition, RRS 1 overexpression was significantly correlated with lymph node metastasis and poor survival. RRS 1 mRNA and protein levels were also significantly increased in a panel of human breast cancer cell lines. RRS 1 knockdown inhibited proliferation and induced apoptosis and cell cycle arrest in all three cell lines. Furthermore, RRS 1 knockdown suppressed the tumour formation and growth of MDA ‐ MB ‐231 cells in nude mice. Additionally, RRS 1 knockdown activated p53 and p21 in MCF ‐7 cells. A marked increase in the quantity of ribosome‐free RPL 11 was detected by Western blot. Moreover, co‐immunoprecipitation (Co IP ) experiments showed that RRS 1 knockdown activated p53 by facilitating the direct contact of MDM 2 and RPL 11/ RPL 5. Taken together, our results suggest that RRS 1 may contribute to breast cancer proliferation through RPL 11/ MDM 2‐mediated p53 activation. Therefore, RRS 1 may be a promising target for breast cancer therapy.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.13922