Abstract 3478: Expression of the transcribed ultraconserved region Uc.63+ in prostate cancer

Abstract

Abstract Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of cancer related death in western world. Currently, there is a lack of effective treatment options for advanced PCa. Understanding the molecular mechanisms in prostate cancer development and progression would allow the identification of novel prognostic markers or therapeutic targets. The transcribed-ultraconserved regions (T-UCRs) are novel class of noncoding RNAs that are absolutely conserved (100%) between orthologous regions of the human, rat and mouse genomes. Some studies showed that T-UCRs exhibit distinct profiles in various human cancers. We examined the expression profile of representative 26 T-UCRs using qRT-PCR in 12 PCa tissues and 10 non-neoplastic prostate tissues, and found that the expression of Uc.63+ was higher in PCa tissues than that in non-neoplastic tissues. Further analysis revealed that the expression of Uc.63+ significantly correlated with higher PSA levels (p = 0.007) and higher Gleason score (p < 0.001). In order to verify biological function of Uc.63+ in PCa, we firstly transfected Uc.63+ expression vector into LNCaP cells expressing low level of Uc.63+. MTT assay and wound healing assay revealed that overexpression of Uc.63+ significantly increased the cell growth and migration. We also confirmed that downregulation of Uc.63+ using siRNA in DU145 and PC3 expressing high level of Uc.63+. Knockdown of Uc.63+ decreased the cell growth and migration. A recent report indicates that T-UCRs may act as endogenous competing RNA. miR-130b was found to have binding sites within the Uc.63+ using online software. We examined the expression of miR-130b by qRT-PCR in PCa tissues and non-neoplastic prostate tissues. We found a significant downregulation of miR-130b in PCa tissues compared with non-neoplastic prostate tissues, which figured out that there was a significant inverse correlation between Uc.63+ and miR-130b in PCa (p = 0.002). The expression of miR-130b in LNCaP was higher than that in DU145 and PC3. It has been shown that MMP2 is a direct target of miR-130b. Western blot analysis and qRT-PCR revealed that MMP2 expression was higher in LNCaP cells transfected with Uc.63+ expression than that in LNCaP cells transfected with empty vector. These results suggest that Uc.63+ may contribute to the progression of PC through miR-130b interaction. Citation Format: Yohei Sekino, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Naoya Sakamoto, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui. Expression of the transcribed ultraconserved region Uc.63+ in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2017-3478