https://orcid.org/0000-0002-8917-284X
Abstract
Introduction
Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE.
Methods
In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (ADARB1, ADAR, ADARB2 and AIMP2) in two independent TACE patient cohorts.
Results
We found that ADARB1 rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in ADARB1 3’-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated ADARB1 levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced ADARB1 expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic ADARB1 profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs.
Discussion
Our findings highlighted the value of ADARB1 polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.
Data Sharing Statement
All data are available on reasonable request from the corresponding authors – Ming Yang; Ziqiang Li.
Ethics Statement
The Ethics Committee of Shandong Cancer Hospital and Institute approved the study (ID: SDCH-JYK-JL-123).
Acknowledgments
We acknowledge all participants enrolled in the study.
Disclosure
The authors report no conflicts of interest in this work.