Downregulation of HBx Restrains Proliferation, Migration, and Invasion of HepG2 Cells

Abstract

Liver cancer is a major contributor to cancer-related death with poor survival for sufferers. Meanwhile, Hepatic B virus X protein (HBx) and XB130 are likely to participate in the pathogenesis of liver cancer. However, the detailed mechanism of HBx/XB130 in liver cancer remains to be further investigated. Our study explored the effects of HBx/XB130 on liver cancer progression. HBx and XB130 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Overexpression of HBx and XB130 was found in liver cancer tissues and cells. Mechanistic study revealed that HBx could bind to and positively regulate XB130 in HepG2 cells. Subsequently, HBx expression was knocked down, while XB130 was overexpressed in HepG2 cells in order to observe the specific role of HBx/XB130 in liver cancer in vitro. Results of CCK-8, Transwell, wound healing, and colony formation assays suggested that HBx could mediate biological function of HepG2 cells by activating the XB130-mediated PI3K/AKT pathway. In summary, our data illustrate that inhibition of HBx effectively suppressed proliferation and metastasis and induced apoptosis of liver cancer cells, which might be partially reversed by XB130. HBx and XB130 may be potential targets for liver cancer pathogenesis.

Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells

“…The high-mobility group box transcription factor 1 (HBP1) has a tumor suppressor function. Cao et al [33] showed that HBP1 inhibits AFP by binding to the affinity site of the AFP promoter. Inhibition of AFP by HBP1 attenuated the effect of AFP on the protein levels of PTEN, matrix metallopeptidase 9 (MMP9) and cysteine-dependent aspartate-specific proteases-3 (caspase-3) in HCC cells.…”

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

“…Hepatitis B virus X protein (HBx) has been found to be overexpressed in liver cancer tissues. 492 It acts as a transcriptional co-activator through direct interaction with various proteins, such as the TATA-binding protein, RPB5 subunit of RNA polymerase II, TF IIH, TF IIB, and the proteins of basic domain-leucine zipper (bZIP) family, including the cyclic AMP-response element (CRE)-binding protein (CREB). 493 HBx interacts with the co-activators CBP/p300 and cooperates with CBP/p300 in the CREB-mediated activation.…”

The pathogenesis of liver cancer and the therapeutic potential of bioactive substances

“…Zhou et al proposed that the HBV X protein captures protons and chloride ions and induces collagen expression in the liver, forming strong hydrogen bonds with the captured protons, and that the HBV X protein and collagen locally accumulate HCl, triggering cirrhosis in some patients The disease progresses to liver cancer ( Zhou et al, 2017 ). HBx can modulate biological processes in HepG2 cells and accelerate the development of HCC by activating the XB130-mediated phosphatidylinositol 3-kinase (PI3K)/AKT pathway ( Huang et al, 2021 ). HBx increases the expression of Smad-interacting protein 1 (SIP1) and recruits it to the promoter of E-cadherin to repress the transcription of E-cadherin, and the consequent decrease in E-cadherin expression blocks intercellular adhesion and attachment, thereby promoting tumor invasiveness ( Ye et al, 2019 ).…”