The role of c-Myc-RBM38 loop in the growth suppression in breast cancer

Li, Xiaoxia; Shi, Liang; Zhou, Xu‐Jie; Wu, Jing; Xia, Tiansong; Zhou, Wenbin; Sun, Xi; Zhu, Lei; Wei, Ji‐Fu; Ding, Qiang

doi:10.1186/s13046-017-0521-5

Cited by 36 publications

(36 citation statements)

References 39 publications

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“…KM plot was shown in Additional file 4 : Figure S3. Many studied found that RBM38 exhibited its tumor growth inhibiting activity by stabilization of p21, p73 and HuR transcripts or destabilization of MDM2 and c-Myc transcripts, via binding to AREs in the 3′-UTR of their mRNAs [ 31 ]. Considering that both PTEN and RBM38 are tumor suppressor genes in breast cancer, we speculated that whether RBM38 functioned as a tumor suppressor by enhancing PTEN expression.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, RBM38 could increase p21, p73, Hu antigen-R (HuR) and growth differentiation factor 15 (GDF15) expressions by stabilizing their mRNAs [ 26 – 28 ]. Conversely, RBM38 could also decrease the stability of p63, c-Myc and mouse double minute 2 homolog (MDM2) by bounding on their mRNA to inhibit tumor cells proliferation [ 29 – 31 ]. In our previous studies, RBM38 was also proved to regulate the expression of ER, and progesterone receptor (PR) by stabilizing their stability to regulate the breast cancer proliferation, both in vivo and vitro [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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

Zhou

Shi

et al. 2017

J Exp Clin Cancer Res

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BackgroundPTEN (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.MethodsImmunohistochemistry, 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.ResultsPTEN 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0620-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhou

Shi

et al. 2017

J Exp Clin Cancer Res

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“…This mechanism of repression is opposite to that exerted by c-Myc in breast cancer context. It has been recently demonstrated that c-Myc represses RNA-binding protein 38 (RBM38) expression through the direct binding of E-box sequences on its promoter [ 38 ]. These data indicate that INI1, when interacts with c-Myc, has an opposite behavior than c-Myc on the c-Myc-related genes.…”

Section: Main Textmentioning

confidence: 99%

Recent advances in searching c-Myc transcriptional cofactors during tumorigenesis

Caforio

Socolovschi²,

Iacovelli

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe mechanism by which c-Myc exerts its oncogenic functions is not completely clear and different hypotheses are still under investigation. The knowledge of the capacity of c-Myc to bind exclusively E-box sequences determined the discrepancy between, on the one hand, genomic studies showing the binding of c-Myc to all active promoters and, on the other hand, the evidence that only 60% or less of the binding sites have E-box sequences.Main bodyIn this review, we provide support to the hypothesis that the cooperation of c-Myc with transcriptional cofactors mediates c-Myc-induced cellular functions. We produce evidence that recently identified cofactors are involved in c-Myc control of survival mechanisms of cancer cells.ConclusionThe identification of new c-Myc cofactors could favor the development of therapeutic strategies able to compensate the difficulty of targeting c-Myc.

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“…We further confirmed that RBM38 could bind to ZO-1 transcript directly by RIP assay. Previous studies found that RBM38 bound to mRNA 3′-UTR of many target genes and altered the stability of the transcripts that all contain multiple AREs ( Zhang et al , 2010 , 2013a ; Yin et al , 2013 ; Cho et al , 2015 ; Li et al , 2017 ). Consistent with this, ZO-1 mRNA 3′-UTR contains several AREs that can be bound by RBPs ( Chen et al , 2008 ; Nagaoka et al , 2012 ).…”

Section: Discussionmentioning

confidence: 99%

RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer

Zhou

Sun

et al. 2017

Br J Cancer

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Background:The transforming growth factor-β (TGF-β) pathway plays a vital role in driving cancer cell epithelial–mesenchymal transition (EMT). Zonula occludens-1 (ZO-1), which is downregulated in response to TGF-β, is able to control endothelial cell–cell tension, cell migration, and barrier formation. However, the molecular mechanism of how TGF-β regulates ZO-1 expression remains unclear.Methods:Breast cancer cells were treated with TGF-β to induce an EMT progress. Chromatin immunoprecipitation and dual-luciferase reporter assay were performed to investigate direct relationship between Snail and RNA binding motif protein 38 (RBM38). The RNA immunoprecipitation combined with RNA electrophoretic mobility shift assay and dual-luciferase reporter assay were conducted to testify direct relationship between RBM38 and ZO-1. The ZO-1 siRNA was transfected to breast cancer cells that overexpress RBM38 and the control, followed by transwell and Matrigel invasion assays to examine cell migratory and invasive ability.Results:Transforming growth factor-β induced a remarkable downregulation of RBM38 in breast cancer that was directly regulated by transcription repressor Snail targeting the E-box elements in promoter region of RBM38 gene. Additionally, RBM38 positively regulated ZO-1 transcript via directly binding to AU/U-rich elements in its mRNA 3′-UTR. Moreover, by magnifying RBM38 expression, cell migration and invasion mediated by knockdown of ZO-1 in breast cancer were reversed.Conclusions:All the results clarified a linear regulation relationship among Snail, RBM38, and ZO-1, implicating RBM38 as a pivotal mediator in TGF-β-induced EMT in breast cancer.

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The role of c-Myc-RBM38 loop in the growth suppression in breast cancer

Cited by 36 publications

References 39 publications

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

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

Recent advances in searching c-Myc transcriptional cofactors during tumorigenesis

RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer

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