Resveratrol limits epithelial to mesenchymal transition through modulation of KHSRP/hnRNPA1-dependent alternative splicing in mammary gland cells

Abstract Long non-coding RNAs (lncRNAs) can affect multiple layers of gene expression to control crucial cellular functions. We have previously demonstrated that the lncRNA EPR, by controlling gene expression at different levels, affects cell proliferation and migration in cultured mammary gland cells and impairs breast tumor formation in an orthotopic transplant model in mice. Here, we used ChIRP-Seq to identify EPR binding sites on chromatin of NMuMG mammary gland cells overexpressing EPR and identified its trans binding sites in the genome. Then, with the purpose of relating EPR/chromatin interactions to the reshaping of the epitranscriptome landscape, we profiled histone activation marks at promoter/enhancer regions by ChIP-Seq. Finally, we integrated data derived from ChIRP-Seq, ChIP-Seq as well as RNA-Seq in a comprehensive analysis and we selected a group of bona fide direct transcriptional targets of EPR. Among them, we identified a subset of EPR targets whose expression is controlled by TGF-β with one of them—Arrdc3—being able to modulate Epithelial to Mesenchymal Transition. This experimental framework allowed us to correlate lncRNA/chromatin interactions with the real outcome of gene expression and to start defining the gene network regulated by EPR as a component of the TGF-β pathway.

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Differential effects of Pax3 on expression of polysialyltransferases STX and PST in TGF-β-treated normal murine mammary gland cells

Experimental Biology and Medicine ◽

10.1177/1535370216669838 ◽

2016 ◽

Vol 242 (2) ◽

pp. 177-183 ◽

Cited By ~ 3

Author(s):

Dong Guo ◽

Jia Guo ◽

Xiang Li ◽

Feng Guan

Keyword(s):

Cell Adhesion ◽

Mammary Gland ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Neural Cell Adhesion Molecule ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Gland Cells ◽

Neural Cell Adhesion ◽

Mammary Gland Cells

Glycosylation of certain proteins at the mammalian cell surface is an essential event in carcinogenesis. Sialylation, one type of glycosylation, can act on multiple cell-behaviors, such as migration, growth, and malignant invasion. Two polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST), are responsible for synthesis of polysialic acid on neural cell adhesion molecule. We showed previously that STX and PST are oppositely expressed in normal murine mammary gland cells undergoing transforming growth factor-β-induced epithelial-mesenchymal transition. The molecular basis for regulation of STX and PST remained unclear. In the present study, we observed that transcription factor Pax3 upregulates STX expression, downregulates PST expression, and modulates upregulated expression of PSA, which attaches primarily to neural cell adhesion molecule to form PSA-NCAM. Overexpression of Pax3 in normal murine mammary gland cells transformed the expression of epithelial-mesenchymal transition markers E-cadherin and N-cadherin, and significantly promoted cell migration, but had no effect on cell proliferation.

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