Abstract
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 there is lack of a clear mechanistic understanding. Androgen receptor (AR) is thought to be critical for such bias. Meanwhile, the potential function of circular RNA (circRNA), regulated by RNA editing enzyme, remained largely unknown in malignancy till now. By utilizing circRNA microarray survey coupled with in vitro analysis, we analyzed the influence of AR on circRNA expression in HCC. Our results indicated that AR could suppress circRNA expression by upregulating ADAR1 p110. Such effect is because AR served as a transcriptional activator of ADAR1 promoter. More significantly, 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 downregulated 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 the roles of circRNA during HCC initiation and progression will provide a novel angle to develop potential HCC therapies.
Highlights
Of all the primary liver cancers, is the second leading cause for cancer-related death worldwide.[1]
In an attempt to examine whether androgen receptor (AR) as a transcription factor 20 can regulate circRNA expression in Hepatocellular carcinoma (HCC), we selected all the verified circRNAs from two previous publications 21,22 and the host gene of these circRNAs would not affected by AR
The results revealed that AR uniformly suppressed expression of this panel of circRNAs whether in the form of overexpressed or knocked down (KD or sh) AR
Summary
Of all the primary liver cancers, is the second leading cause for cancer-related death worldwide.[1]. 000 patients died of HCC.[2] In our center, only limited number of HCC patients qualified for primary resection or liver transplantation as a curative procedure for HCC treatment, and similar dilemma is encountered all over the world.[3,4]. Salvage chemotherapy has limited options with the recent addition of Sorafenib as the only one proved by the Food and. A better understanding of the HCC initiation and progression will likely provide novel and efficacious treatment for HCC.[9] The role of androgen receptor (AR) in gender disparity of HCC during initiation and progression has been well documented, yet application of that knowledge has not been successful in providing therapies for HCC.[10,11]. ADAR1 was reported to be a critical regulator of circRNA formation.[19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
