BORIS variant SF2(C2/A4) promotes the malignant development of liver cancer by activating epithelial‐mesenchymal transition and hepatic stellate cells

• DOI: 10.1002/mc.23520
• Publication Date: 2023-03-17T08:59:26Z
• Authors: Ling Wei; Zhongjian Liu; Lu Qin; Longjun Xian; Kefei Chen; Siqi Zhou; Lei Hu; Yimei Xiong; Bo Li; Yang Qin
• Keywords: Hepatic stellate cell

Abstract The underlying mechanisms of metastasis and recurrence liver cancer remain largely unknown. Here, we found that Brother the Regulator Imprinted Sites (BORIS) variant SF2(C2/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells clinical tumor samples, related to formation satellite nodules. Its over expression promoted self‐renewal, stem cell markers, chemoresistance, wound healing rate, invasion HepG2 Hep3B cells; reinforced epithelial‐mesenchymal transition (EMT), decreased E‐cadherin increased N‐cadherin Vimentin. Subcellular localization experiment showed BORIS localized nucleus cytoplasm. Further double luciferase reporter gene confirmed it bound TWIST1 promoter significantly latter expression. knock down induced apoptosis HCCLM3 PLC/PRF/5 cells, protein content cleaved caspase 3. Additionally, fibroblast growth factor 2 (FGF2) cells. FGF2 higher HCC tissues than paired peri‐tumor tissues, its positively correlated with SF2(C2/A4). Interestingly, is also associated Moreover, using medium from overexpressed lines coculture hepatic stellate (HSCs) line LX‐2, could be activated CD90 PIGF, which consistent effect adding bFGF alone. These results indicate plays a role deterioration by regulating induce EMT, activate HSCs.