Tissue-Specific Target Analysis of Disease-Associated MicroRNAs in Human Signaling Pathways

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

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Akt3 Regulates the Tissue-Specific Response to Copaiba Essential Oil

International Journal of Molecular Sciences ◽

10.3390/ijms21082851 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2851

Author(s):

Yasuyo Urasaki ◽

Cody Beaumont ◽

Jeffery N. Talbot ◽

David K. Hill ◽

Thuc T. Le

Keyword(s):

Essential Oil ◽

Signaling Pathways ◽

Signaling Pathway ◽

Liver Cells ◽

Mtor Signaling ◽

Specific Response ◽

Mtor Signaling Pathway ◽

Tissue Specific ◽

Regulatory Effects ◽

Specific Regulation

This study reports a relationship between Akt3 expression and tissue-specific regulation of the pI3K/Akt/mTOR signaling pathway by copaiba essential oil. Akt3, a protein kinase B isoform important for the regulation of neuronal development, exhibited differential expression levels in cells of various origins. In neuronal and microglial cells, where Akt3 is present, copaiba essential oil positively regulated the pI3K/Akt/mTOR signaling pathway. In contrast, in liver cells and T lymphocytes, where Akt3 is absent, copaiba essential oil negatively regulated the pI3K/Akt/mTOR signaling pathway. The expression of Akt3 via plasmid DNA in liver cells led to positive regulatory effects by copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. In contrast, inhibition of Akt3 expression in neuronal cells via small interfering RNA molecules targeting Akt3 transcripts abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Interestingly, Akt3 expression did not impact the regulatory effects of copaiba essential oil on other signaling pathways. For example, copaiba essential oil consistently upregulated the MAPK and JAK/STAT signaling pathways in all evaluated cell types, independent of the Akt3 expression level. Collectively, the data indicated that Akt3 expression was required for the positive regulatory effects of copaiba essential oil, specifically on the pI3K/Akt/mTOR signaling pathway.

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Tissue-specific transcripts of human steroid sulfatase are under control of estrogen signaling pathways in breast carcinoma

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2006.12.101 ◽

2007 ◽

Vol 105 (1-5) ◽

pp. 76-84 ◽

Cited By ~ 20

Author(s):

Tetiana Zaichuk ◽

David Ivancic ◽

Denise Scholtens ◽

Carol Schiller ◽

Seema A. Khan

Keyword(s):

Breast Carcinoma ◽

Signaling Pathways ◽

Estrogen Signaling ◽

Steroid Sulfatase ◽

Tissue Specific

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Engineering combinatorial and dynamic decoders using synthetic immediate-early genes

10.1101/2019.12.17.880179 ◽

2019 ◽

Author(s):

Pavithran T. Ravindran ◽

Maxwell Z. Wilson ◽

Siddhartha G. Jena ◽

Jared E. Toettcher

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Intracellular Signaling ◽

Target Genes ◽

Immediate Early Genes ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Specific Target ◽

Early Genes

AbstractFor tissues to grow and function properly, cells must coordinate actions such as proliferation, differentiation and apoptosis. This coordination is achieved in part by the activation of intracellular signaling pathways that trigger the expression of context-specific target genes. While the function of these natural circuits has been actively studied, synthetic biology provides additional powerful tools for deconstructing, repurposing, and designing novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (synIEGs), target genes of the Erk signaling pathway that implement complex, user-defined regulation and can be monitored through the use of live-cell biosensors to track transcription and translation. We demonstrate the power and flexibility of this approach by confirming Erk duration-sensing by the FOS immediate-early gene, elucidating how the BTG2 gene is regulated by transcriptional activation and translational repression after growth-factor stimulation, and by designing a synthetic immediate-early gene that responds with AND-gate logic to the combined presence of growth factor and DNA damage stimuli. Our work paves the way to defining the molecular circuits that link signaling pathways to specific target genes, highlighting an important role for post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.

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