Abstract
Though it is widely known that hepatitis B virus X protein (HBx) is involved in the progression of hepatocellular carcinoma (HCC), the underlying mechanisms are not entirely clear. In recent years, metastasis associated with lung adenocarcinoma transcript 1 (MALAT1), which is an oncogenic long non-coding RNA (lncRNA), has been proved to be associated with many kinds of tumors, including liver cancer. In this study, we demonstrated that MALAT1 was involved in the HBx-mediated hepatocarcinogenesis. Firstly, we found that expression of MALAT1 was strongly up-regulated in HCC tissues and was directly proportional to the expression of HBx. Moreover, in HBx transfected LO2 and HepG2 cells, MALAT1 was also up-regulated compared with non-transfected cells. Then, we observed up-regulated MALAT1 in HepG2 cells could promote cell invasion and migration, whereas knockdown of MALAT1 in HBx-expressing hepatic cells (HepG2-HBx) resulted in a markedly inhibition of cell invasion and migration both in vitro and in vivo. To further obtain a deeper understanding of the effect of MALAT1, we took latent transforming growth factor β-binding protein 3 (LTBP3) into account by using several assays such as RNA interference, luciferase, transwell and wound healing. Results showed that MALAT1 could promote tumor growth and metastasis by activating LTBP3, which could also be up-regulated by HBx. Meanwhile, the similar results were detected in nude mice. These findings could demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-MALAT1/LTBP3 axis, and may give a potential target for treatment of HCC.