MiR-30e* is overexpressed in prostate cancer and promotes NF-?B-mediated proliferation and tumor growth.

ABSTRACT: According to the CDC prostate cancer (CaP) has the highest incidence and second highest mortality rate amongst cancers in American men. Constitutive NF-?B 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-?B gene signature is predictive of CaP progression and biochemical recurrence following therapeutic intervention. However, the mechanisms that perpetuate NF-?B activation are incompletely understood. Genes that control NF-?B activity are rarely mutated in CaP suggesting that epigenetic mechanisms may contribute to constitutive NF-?B activation. microRNAs (miRs) epigenetically regulate many genes involved with NF-?B activation. I?B? is a direct inhibitor of NF-?B; it binds to and sequesters NF-?B in the cytoplasm resulting in functional inhibition. I?B? 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 I?B?, which results in chronic activation of NF-?B. 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.

SUBMITTER: Egan SM 

PROVIDER: S-EPMC5620198 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature