miR-30e* is overexpressed in prostate cancer and promotes NF-κB-mediated proliferation and tumor growth
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Shawn M. Egan1, Ellen Karasik2, Leigh Ellis3 and Sandra O. Gollnick4
1Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
2Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
3Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
4Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
Sandra O. Gollnick, email: Sandra.firstname.lastname@example.org
Keywords: NF-κB, microRNA, prostate cancer, cyclin D1
Received: December 30, 2015 Accepted: June 02, 2017 Published: June 28, 2017
According to the CDC prostate cancer (CaP) has the highest incidence and second highest mortality rate amongst cancers in American men. Constitutive NF-κB activation is a hallmark of CaP and this pathway drives many pro-tumorigenic characteristics of CaP cells, including cell proliferation and survival. An activated NF-κB gene signature is predictive of CaP progression and biochemical recurrence following therapeutic intervention. However, the mechanisms that perpetuate NF-κB activation are incompletely understood. Genes that control NF-κB activity are rarely mutated in CaP suggesting that epigenetic mechanisms may contribute to constitutive NF-κB activation. microRNAs (miRs) epigenetically regulate many genes involved with NF-κB activation. IκBα is a direct inhibitor of NF-κB; it binds to and sequesters NF-κB in the cytoplasm resulting in functional inhibition. IκBα is a target gene of miR-30e* yet the expression and oncological impact of miR-30e* in CaP is unknown. We report that miR-30e* expression is elevated in multiple murine models of CaP and is most pronounced in late stage disease. miR-30e* drives CaP proliferation and tumor growth through inhibition of IκBα, which results in chronic activation of NF-κB. Additionally, we show that inhibition of miR-30e* improves chemotherapeutic control of CaP. Thus, miR-30e* may prove to be a novel clinical target whose inhibition leads to decreased CaP cell proliferation and sensitization of CaP cells to chemotherapeutics.
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