Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Abstract The treatment of triple-negative breast cancer (TNBC) relies largely on chemotherapies. However, it is frequent that TNBC patients develop resistance to the chemotherapy drugs. Generation of drug-resistant cell lines facilitates the identification of drug resistance. Here, we established two paclitaxel (PTX)-resistant TNBC cancer cell lines using an intermittent and stepwise method and found that long non-coding RNA long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) was significantly decreased in PTX-resistant cancer cells. Ectopic expression of LINC-PINT sensitized both PTX-resistant TNBC and wild-type TNBC to PTX. Moreover, RNA immunoprecipitation showed that LINC-PINT bound to RNA-binding protein NONO. Overexpression of LINC-PINT resulted in the degradation of NONO in a proteasome-dependent manner and vice versa. Knockdown of NONO with siRNA sensitized TNBC to PTX. We further analyzed the expression level of LINC-PINT and NONO in patient samples via online database and found that LINC-PINT and NONO may function antagonistically in all types of breast cancers. Taken together, our data illustrated a tumor suppressor role of LINC-PINT in sensitizing TNBC to chemotherapies via destabilizing NONO.

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RNA-binding protein MSI2 isoforms expression and regulation in progression of triple-negative breast cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01587-x ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Ming Li ◽

An-qi Li ◽

Shu-ling Zhou ◽

Hong Lv ◽

Ping Wei ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein

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Abstract P5-05-09: Chemo-sensitization of triple negative breast cancer by targeting RNA-binding protein HuR

10.1158/1538-7445.sabcs19-p5-05-09 ◽

2020 ◽

Author(s):

Xiaoqing Wu ◽

Lanjing Wei ◽

Gulhumay Gardashova ◽

Cuncong Zhong ◽

Lan Lan ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein

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Effect of RNA-binding protein MSI2 deficiency on progression in triple-negative breast cancer via stabilizing TP53INP1.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12555 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12555-e12555

Author(s):

Ping Wei ◽

Ming Li ◽

Wentao Yang ◽

Xiaoyan Zhou

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Cell Invasion ◽

Triple Negative ◽

Rna Binding ◽

Rna Binding Protein ◽

Normal Tissues ◽

Tnbc Cell ◽

Proliferation And Invasion

e12555 Background: The RNA-binding protein Musashi-2 (MSI2) has been implicated in the tumorigenesis and tumor progression of human cancers. This study investigated the clinical significance of MSI2 and the potential molecular mechanisms involved in triple-negative breast cancer (TNBC) progression. Methods: The Illumina sequencing platform was used to analyze the mRNA transcriptome in TNBC vs. normal tissues, while quantitative reverse transcription–polymerase chain reaction and immunohistochemistry validated MSI2 expression in breast cancer tissues and the effects of MSI2 on TNBC cells were assayed in vitro and in viv o. RNA immunoprecipitation (RIP) DNA and RNA sequencing was performed to identify the potential MSI2-targeted mRNAs. RIP and luciferase analyses were used to confirm the mRNA targets of MSI2. Results: MSI2 expression was significantly downregulated in TNBC vs. normal tissues and was associated with a poor overall survival of patients. MSI2 overexpression in vitro and in vivo inhibited TNBC cell proliferation and invasion as well as the extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Molecularly, MSI2 expression promoted the stability of TP53INP1 mRNA by its interaction with the TP53INP1 mRNA 3ʹ-untranslated region. Furthermore, knockdown of TP53INP1 expression was able to reverse MSI2-induced suppression of TNBC cell invasion, whereas ectopic expression of TP53INP1 and inhibition of the ERK1/2 activity blocked MSI2 knockdown-induced TNBC cell invasion. Conclusions: The current study demonstrated that downregulated MSI2 expression was associated with TNBC progression and a poor prognosis and that MSI2 expression inhibited TNBC proliferation and invasion by induction of TP53INP1 stability and inhibition of ERK1/2 activity.

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