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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2017 | Research

PTEN expression is upregulated by a RNA-binding protein RBM38 via enhancing its mRNA stability in breast cancer

Authors: Xu-Jie Zhou, Jing Wu, Liang Shi, Xiao-Xia Li, Lei Zhu, Xi Sun, Jia-Yi Qian, Ying Wang, Ji-Fu Wei, Qiang Ding

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

Abstract

Background

PTEN (phosphatase and tensin homolog gene on chromosome 10), a well-characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal. PTEN expression is closely related to the phenotype, prognosis and drug selection in breast cancer. It is mainly regulated by transcriptional and post-transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA-binding protein (RBP) and a target of P53 family, plays a crucial role in the regulation of cellular processing, especially in post-transcription regulation and gene transcription. In this study, we investigated a new post-transcription regulation mechanism of PTEN expression by RBM38 in breast cancer.

Methods

Immunohistochemistry, lentivirus transfections, Western blotting analysis, qRT-PCR and ELISA were used to conduct the relation between RBM38 and PTEN. RNA immunoprecipitation, RNA electrophoretic mobility shift and dual-luciferase reporter assays were employed to identify the direct binding sites of RBM38 with PTEN transcript. Colony formation assay was conducted to confirm the function of PTEN in RBM38-induced growth suppression.

Results

PTEN expression was positively associated with the expression of RBM38 in breast cancer tissues and breast cancer cells. Moreover, RBM38 stabilized PTEN transcript to enhance PTEN expression via binding to multiple AU/U- rich elements (AREs) in 3′-untranslated region (3′-UTR) of PTEN transcript. Additionally, specific inhibitors of PTEN activity and small interfering (siRNA) of PTEN expression inhibited RBM38-mediated suppression of proliferation, which implied that RBM38 acted as a tumor suppressor partly by enhancing PTEN expression.

Conclusion

The present study revealed a new PTEN regulating mechanism that PTEN was positively regulated by RBM38 via stabilizing its transcript stability, which in turn alleviated RBM38-mediated growth suppression.

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Title: PTEN expression is upregulated by a RNA-binding protein RBM38 via enhancing its mRNA stability in breast cancer
Authors: Xu-Jie Zhou
Jing Wu
Liang Shi
Xiao-Xia Li
Lei Zhu
Xi Sun
Jia-Yi Qian
Ying Wang
Ji-Fu Wei
Qiang Ding
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-017-0620-3

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