Abstract 1814: Carboxyl-terminal truncated HBx represses lncRNA-LOC to promote cell metastasis

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancy in the world. The poor prognosis of HCC is partly due to a high incidence rate of extrahepatic metastases. Several studies have shown that the relative risk of HCC among hepatitis B virus (HBV) carrier is higher than non-carrier group. Among the four proteins translated by HBV, X-gene (HBx) has been correlated with oncogenesis of HCC. Meanwhile, it is well known that random HBV genome integration can cause truncation of the HBV genome, especially on the HBx gene locus at the C-terminus (designated as Ct-HBx). The discovery of long non-coding RNA (lncRNA) transcripts has dramatically expanded our understanding of cell biology, especially in cancer. However, the underlying molecular mechanisms of lncRNAs that mediate the metastatic cascade and cancer progression remain largely unclear in liver cancer. In this study, lncRNA-LOC is significantly downregulated in HCC and negatively correlated with overall survival in HCC patients. LncRNA-LOC is negatively regulated by Ct-HBx in vitro and in vivo (HCC specimens). Two novel transcripts of LncRNA-LOC in HepG2 and Huh7 cell lines were identified by 5’ and 3’ rapid amplification of cDNA ends assays, respectively. Overexpression of lncRNA-LOC induced marked inhibition of cell migration, invasion and cell proliferation in vitro. On the other hand, these phenotypes were reversed upon knockdown of lncRNA-LOC in cells. Mechanically, levels of p-STAT3 (Tyr705 and Ser727), p-c-Jun (Ser63) and Snail were decreased in lncRNA-LOC-overexpressing cells, compared to control cells. Our data collectively highlight that novel regulatory associations among lncRNA-LOC, Ct-HBx, p-STAT3, p-c-Jun and Snail are an important determinant of metastasis in HCC cells and support the potential utility of lncRNA-LOC as a therapeutic strategy for HCC. Citation Format: Yang Hsiang Lin, Chau-Ting Yeh, Kwang-Huei Lin. Carboxyl-terminal truncated HBx represses lncRNA-LOC to promote cell metastasis [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 1814.