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MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
MicroRNA miR-155 inhibits bone morphogenetic protein (BMP) signaling and BMP-mediated Epstein-Barr virus reactivation
Qinyan Yin1, Xia Wang, Claire Fewell
1Tulane Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Abstract:
MicroRNA miR-155 is expressed at elevated levels in human cancers including cancers of the lung, breast, colon, and a subset of lymphoid malignancies. In B cells, miR-155 is induced by the oncogenic latency gene expression program of the human herpesvirus Epstein-Barr virus (EBV). Two other oncogenic herpesviruses, Kaposi's sarcoma-associated herpesvirus and Marek's disease virus, encode functional homologues of miR-155, suggesting a role for this microRNA in the biology and pathogenesis of these viruses. Bone morphogenetic protein (BMP) signaling is involved in an array of cellular processes, including differentiation, growth inhibition, and senescence, through context-dependent interactions with multiple signaling pathways. Alteration of this pathway contributes to a number of disease states including cancer. Here, we show that miR-155 targets the 3' untranslated region of multiple components of the BMP signaling cascade, including SMAD1, SMAD5, HIVEP2, CEBPB, RUNX2, and MYO10. Targeting of these mediators results in the inhibition of BMP2-, BMP6-, and BMP7-induced ID3 expression as well as BMP-mediated EBV reactivation in the EBV-positive B-cell line, Mutu I. Further, miR-155 inhibits SMAD1 and SMAD5 expression in the lung epithelial cell line A549, it inhibits BMP-mediated induction of the cyclin-dependent kinase inhibitor p21, and it reverses BMP-mediated cell growth inhibition. These results suggest a role for miR-155 in controlling BMP-mediated cellular processes, in regulating BMP-induced EBV reactivation, and in the inhibition of antitumor effects of BMP signaling in normal and virus-infected cells.
Insights
MicroRNA miR-155 targets bone morphogenetic protein (BMP) signaling components, inhibiting BMP
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- MicroRNA miR-155 is upregulated in various human cancers, including lung, breast, and colon.
- miR-155 is induced by Epstein-Barr virus (EBV) in B cells, and related microRNAs are encoded by other oncogenic herpesviruses.
- Bone morphogenetic protein (BMP) signaling regulates cellular processes like differentiation and growth inhibition, and its dysregulation is linked to cancer.
Purpose of the Study:
- To investigate the role of miR-155 in targeting BMP signaling components.
- To determine the impact of miR-155 on BMP-mediated cellular processes and EBV reactivation.
- To explore miR-155's influence on the antitumor effects of BMP signaling.
Main Methods:
- Analysis of miR-155 targeting of BMP signaling components (SMAD1, SMAD5, HIVEP2, CEBPB, RUNX2, MYO10) in their 3' UTR.
- Assessment of miR-155's effect on BMP-induced ID3 expression and EBV reactivation in EBV-positive B cells (Mutu I).
- Evaluation of miR-155's impact on BMP-mediated p21 induction and cell growth inhibition in lung epithelial cells (A549).
Main Results:
- miR-155 directly targets multiple BMP signaling mediators, inhibiting BMP2-, BMP6-, and BMP7-induced ID3 expression.
- miR-155 inhibits BMP-mediated EBV reactivation in Mutu I cells and suppresses SMAD1/SMAD5 expression in A549 cells.
- miR-155 reverses BMP-mediated cell growth inhibition and induction of the cyclin-dependent kinase inhibitor p21.
Conclusions:
- miR-155 plays a significant role in modulating BMP-mediated cellular processes.
- miR-155 regulates BMP-induced EBV reactivation, suggesting a link between viral latency and host signaling.
- miR-155 inhibits the antitumor effects of BMP signaling, potentially contributing to cancer development and progression.
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