Abstract 1902: Downregulation of MYC by miR-3189-3p in glioblastoma

Abstract

Abstract Glioblastoma is a devastating malignancy with a median survival of approximately 15 months. This aggressive tumor originates from the glial cells and accounts for nearly 50% of adult brain tumors. Glioblastomas are characterized by rapid proliferation and resistance to standard treatment of surgery, temazolamide and radiation therapy. MicroRNAs are short single-stranded non-coding RNAs that regulate gene expression in both normal and pathological conditions. We have previously found downregulation of miR-3189-3p in glioblastomas and astrocytomas. Using in vitro models, we demonstrated that ectopic expression of this miRNA inhibited glioblastoma cell growth and migration through downregulation of the splicing factor SF3B2 and the guanine nucleotide exchange factor p63RhoGEF, respectively. The miR-3189-3p-mediated inhibition of glioblastoma growth in vivo further confirmed the anti-cancer activity of this microRNA. Given the strong biological effect of this miRNA on glioblastoma cells, we sought to investigate the implication of other gene targets in miR-3189-3p-mediated effects. The elevated expression of MYC oncogene is found in a variety of cancer types, including glioblastoma. Here, we demonstrated that overexpression of miR-3189-3p results in downregulation of MYC. Since this gene is not a predicted target for miR-3189-3p, we hypothesized that this modulation of MYC expression is mediated through the translational repressor, TIA1 cytotoxic granule-associated RNA binding protein-like 1 (TIAL1, also called TIAR). We tested the levels of TIAR in cells treated with miR-3189-3p and found no changes in TIAR expression. However, the downregulation of MYC was dependent on TIAR expression, as determined through siRNA-mediated downregulation of TIAR. Further studies are needed to elucidate molecular mechanisms of TIAR-dependent downregulation of MYC by miR-3189-3p. In addition, a putative binding site for miR-3189-3p is located within the open reading frame of MYC; therefore, studies will be performed to determine whether miR-3189-3p downregulates MYC by directly binding outside the 3’-UTR of this transcript. Citation Format: Duane Jeansonne, Krzysztof Reiss, Francesca Peruzzi. Downregulation of MYC by miR-3189-3p in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1902.