Abstract 1823: SNORD78 promotes prostate cancer progression and regulates AR expression and signaling

Abstract

Abstract While small nucleolar RNAs (snoRNAs) have long been thought of as housekeeping genes, emerging evidence now suggests that snoRNAs are involved in more than previously thought and also in the development of disease. In cancer, it is understood that snoRNA expression and function can be altered, but little is known regarding the role of snoRNAs in these diseases. SNORD78 is a C/D box snoRNA which has been shown to be overexpressed in prostate cancer and associated with disease progression. However, there are no studies functionally characterizing SNORD78 in prostate cancer. In this study we sought to understand the functional contribution of SNORD78 in prostate cancer progression. Oncomine was used to assess SNORD78 expression in clinical prostate cancer samples. LNCaP and C4-2B prostate cancer cell lines were used. We used siRNAs to inhibit SNORD78 expression and cell viability assays to assess cell growth. ELISAs were used to assess PSA secretion and cell death. Western blots and quantitative PCR were used to assess cell death (PARP-cleavage) and AR expression and signaling. We found that SNORD78 expression was up-regulated in prostate tumors and associated with metastatic progression. Cell viability assays demonstrated that inhibition of SNORD78 expression resulted in a drastic reduction in prostate cancer cell growth and lower secretion of PSA into the media. Cell death ELISAs and western blots for cleaved-PARP showed that SNORD78 inhibition induced robust apoptosis in both LNCaP and C4-2B cells. As the androgen receptor (AR) is the primary target for prostate cancer therapy, we tested whether SNORD78 regulated AR expression and signaling. Inhibition of SNORD78 in both LNCaP and C4-2B cells resulted in reduced AR mRNA and protein levels. We also found that SNORD78 knockdown led to decreased levels of PSA and NKX3.1, suggesting that AR downstream signaling was inhibited. Our findings suggest that SNORD78 promotes prostate cancer cell viability and disease progression. We also demonstrate that SNORD78 regulates the AR and may be involved in promoting AR signaling needed for prostate cancer cell survival. Collectively, these data suggest that SNORD78 plays a critical role in prostate cancer progression and may represent a novel therapeutic target. Citation Format: Alan P. Lombard, Chengfei Liu, Cameron M. Armstrong, Leandro S. D'Abronzo, Wei Lou, Christopher P. Evans, Allen C. Gao. SNORD78 promotes prostate cancer progression and regulates AR expression and signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1823.