Circular RNA Expression is Suppressed by Androgen Receptor (AR) Regulated Adenosine DeAminase that act on RNA (ADAR1) in Human Hepatocellular Carcinoma. Homo sapiens

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy as a result of complex genetic and epigenetic alterations. HCC is characterized by a clear gender disparity for which lacking a clear mechanistic understanding. By utilizing circular RNA (circRNA) microarray survey coupled with in vitro analysis, we analyzed the influence of androgen receptor (AR) on circRNA expression in HCC. Our results indicated that AR could suppress circRNA expression by up-regulating adenosine deaminase that act on RNA (ADAR1) p110 at a transcriptional level. Reporter assay further confirmed the role of AR as a transcriptional activator of ADAR1 expression. Furthermore, data collected from our center strongly suggest that ADAR1 expression can effectively predict HCC patients’ prognosis and an abnormal overexpression of ADAR1 is positively correlated with AR in HCC. In addition, we found CircARSP91 (hsa_circ_0085154), one of the circRNAs down-regulated by AR in an ADAR1-dependent manner, could inhibit HCC tumor growth both in vitro and in vivo. These findings highlight the fact that AR as a contributing factor for gender disparity in HCC can cause complex consequences though regulation of circRNA expression. Better understanding of roles of circRNA during HCC initiation and progression will be a key to develop novel HCC therapies. Overall design: [i] We detected the circular RNA expression profile of shAR-MHCC-97H (named as s97H.shAR) and shScr-MHCC-97H (named as s97H.PLKO). The stable transfected cells was established by using lenti-virus system. The knocking-down or overexpression efficiency was verified on both mRNA level and protein level. [ii] We detected the circular RNA expression profile of oeAR-LO2 (named as LO2.AR) and vector-LO2 (named as LO2.PWPI). The stable transfected cells was established by using lenti-virus system. The knocking-down or overexpression efficiency was verified on both mRNA level and protein level.