Abstract
Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with a very poor prognosis, which is closely associated with cancer stem cell (CSC). Global RNA-sequencing was used in different developmental stages of hepatocytes, including embryonic stem cell, endoderm, liver progenitor, and premature hepatocyte, as well as two pairs of nontumor and tumor tissues from HCC patients. We found that Developmental Pluripotency Associated 3 (DPPA3) was highest expressed in the stage of liver progenitor cells, and was down-regulated along with development. In HCC patients, DPPA3 was expressed in less than 1% tumor cells, while no staining was detected in normal counterparts. Functional assays revealed that DPPA3 overexpression increased HCC cells proliferation rate, the ability of foci formation and colony formation in soft agar, as well as migration and invasion. Furthermore, DPPA3 significantly increased HCC cells sphere formation frequency and sensitivity to chemotherapeutic agent including cisplatin, 5-Fu, and Sorafenib. In order to investigate the role of DPPA3 in CSC maintenance and stemness regulation in HCC, whole genome methylation sequencing was applied to compare methylation status between DPPA3- and empty vector-transfected cells. Results showed that DPPA3 reduced CG methylation level within functional regions in the genome. Of the 541 differentially methylated regions, the majority of them were involved in developmental process and cell differentiation. Overall, our findings give a novel insight into how methylation regulation controls the fate of cancer stem cells. Citation Format: Qian Yan, Yu Zhang, Dandan Yu, Ngar Woon Kam, Xin-Yuan Guan. Characterization of the role of DPPA3 in stemness regulation in hepatocellular carcinoma by DNA methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2490.
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