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  • Title: MicroRNA-146a targets PRKCE to modulate papillary thyroid tumor development.
    Author: Zhang X, Li D, Li M, Ye M, Ding L, Cai H, Fu D, Lv Z.
    Journal: Int J Cancer; 2014 Jan 15; 134(2):257-67. PubMed ID: 23457043.
    Abstract:
    MicroRNAs are single-stranded noncoding RNAs composed of approximately 22 nucleotides that suppress gene expression by selectively binding via base-pairing to the complementary 3'-untranslated region (3'-UTR) of messenger RNA transcripts. Protein kinase C epsilon (PKCε) is an important modulating member of the transducing Ras/Raf-1 signal pathway; a computational search revealed miR-146a putatively binds to the 3'-UTR of the PRKCE gene, and thus decreasing PKCε expression. Moreover, PKCε inhibits mitochondrial apoptosis and is associated with the Bcl family. However, it has been previously reported that miR-146a expression in papillary thyroid carcinoma (PTC) is slightly elevated. Thus, we hypothesized that because miR-146a expression depends on nuclear factor kappaB (NF-κB) activation and NF-κB expression is elevated in PTC, miR-146a is potentially upregulated in PTC via negative feedback of NF-κB, and thus suppressing PKCε expression. In our study, we investigated whether overexpression of miR-146a, a tumor-suppressing-miR, in PTC cells decreases cell survival and induces apoptosis. Luciferase reporter assay analysis confirmed the direct binding of miR-146a and PRKCE 3'-UTR. Specific overexpression of exogenous miR-146a significantly decreased PKCε levels in PTC cell line NPA-187 and increased apoptosis. Additionally, using stably expressing miR-146a thyroid carcinoma cells to establish subcutaneous tumors, the tumor growth exhibited significant inhibition. Our study confirmed the tumor-suppressing role of miR-146a in thyroid carcinoma cells and contributes to the knowledge regarding modulation of Ras/Raf-1 signal transduction and apoptosis via PKCε targeted by miR-146a in PTC; moreover, our findings confirmed that miR-146a is involved in the feedback system of the classical NF-κB signal pathway in PTC.
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