Browsing by Subject "Oncogene"

Now showing 1 - 2 of 2
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    Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity
    (Springer Nature, 2018-06) Özeş, Ali R.; Pulliam, Nick; Ertosun, Mustafa G.; Yilmaz, Özlem; Tang, Jessica; Çopuroğlu, Ece; Matei, Daniela; Özeş, Osman N.; Nephew, Kenneth P.; Cellular and Integrative Physiology, School of Medicine
    Polycomb Repressive Complex 2 (PRC2) member enhancer of zeste homologue 2 (EZH2) trimethylates histone H3 lysine 27 (H3K27me3), alters chromatin structure and contributes to epigenetic regulation of gene expression in normal and disease processes. Phosphorylation of EZH2 augmented EZH2 oncogenic activity in cancer but observations have been limited to serine 21 (S21) residue by protein kinase B. In addition, phosphorylation of the evolutionarily conserved T372 motif of EZH2 by p38 resulted in EZH2 interaction with Ying Yang 1 and promoted muscle stem cell differentiation. In the present study, we used epithelial ovarian cancer (OC) cells as a model to demonstrate that phosphorylation of EZH2 at T372 by protein kinase A (PKA) induced a dominant-negative EZH2 phenotype, inhibited OC cell proliferation and migration in vitro and decreased ovarian xenograft tumor growth in vivo. Phosphorylation of T372 by PKA enhanced the interaction between EZH2 and signal transducer and activator of transcription 3 (STAT3), and STAT3 binding to pT372-EZH2 reduced cellular levels of pSTAT3 and downregulated interleukin 6 receptor expression in OC. Furthermore, PKA-mediated pT372-EZH2 decreased ATP levels and altered mitochondrial gene expression, resulting in mitochondrial dysfunction and reduced OC cell growth. These findings demonstrate that PKA-mediated T372 phosphorylation reduces oncogenic EZH2 activity and reveal a novel role for pT372 in regulating EZH2 in OC and possibly other cancers.
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    A Systematic Review of miR-29 in Cancer
    (Elsevier, 2018-12-31) Kwon, Jason J.; Factora, Tricia D.; Dey, Shatovisha; Kota, Janaiah; Medical and Molecular Genetics, School of Medicine
    MicroRNAs (miRNA) are small non-coding RNAs (∼22 nt in length) that are known as potent master regulators of eukaryotic gene expression. miRNAs have been shown to play a critical role in cancer pathogenesis, and the misregulation of miRNAs is a well-known feature of cancer. In recent years, miR-29 has emerged as a critical miRNA in various cancers, and it has been shown to regulate multiple oncogenic processes, including epigenetics, proteostasis, metabolism, proliferation, apoptosis, metastasis, fibrosis, angiogenesis, and immunomodulation. Although miR-29 has been thoroughly documented as a tumor suppressor in the majority of studies, some controversy remains with conflicting reports of miR-29 as an oncogene. In this review, we provide a systematic overview of miR-29's functional role in various mechanisms of cancer and introspection on the contradictory roles of miR-29.