UHRF2 promotes migration and proliferation of human hepatocellular carcinoma cells by PI3K/Akt signaling pathway

• Main Authors: CHENG Fengjuan, SUN Jingjie, FANG Xianyun, CHEN Siyuan, LIU Shangjing
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2020-07-01
• Series: Di-san junyi daxue xuebao
• Subjects: hepatocellular carcinoma; uhrf2; cell migration; cell proliferation; pi3k/akt signaling pathway
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/202002072.htm

Objective To explore the role of Ubiquitin-like with PHD and RING finger domains 2 (UHRF2) on the migration and proliferation of human hepatocellular carcinoma (HCC) cells and investigate its underlying mechanism. Methods The HCC gene expression data and patient clinical data were searched in the TCGA database, the differences of UHRF2 expression were analyzed between normal liver tissue and HCC tissue, and the correlation of its level with prognosis was also analyzed. Liver tumor tissues and adjacent normal tissues were harvested from 20 HCC patients diagnosed in the First Affiliated Hospital of Chongqing Medical University between July, 2008 and December, 2013 to detect UHRF2 expression by immunohistochemistry. The relationship between UHRF2 expression and clinical pathological parameters of these patients was analyzed. After UHRF2 expression plasmid was constructed and transfected into HepG2 and HepG2.2.15 cells, the transfection efficiency was measured by RT-qPCR and Western blotting. Then cell scratch test and plate cloning was employed to detect the effect of UHRF2 overexpression on the migration and proliferation of the cells. Gene set enrichment analysis was applied to further explore the relationship between UHRF2 and activation of PI3K/Akt signaling pathway. The expression of Akt, PI3K, p-Akt and p-PI3K was detected with Western blotting. Results TCGA database analysis revealed that the expression of UHRF2 in HCC tissues was higher than that in normal liver tissues, and indicated a poor prognosis. Cox multivariate regression analysis found that UHRF2 expression was an independent risk factor for the prognosis. Immunohistochemistry showed that the expression level of UHRF2 was significantly higher in the HCC tissues than that in the adjacent normal tissues. The high expression of UHRF2 was closely related to tumor size (P=0.002) and tumor metastasis (P=0.002). In wound healing test and plate cloning test, the HCC cells with UHRF2 overexpression showed significantly stronger migration and proliferation abilities as compared with the control cells. PI3K/Akt pathway was significantly enriched in the HCC patients with higher expression of UHRF2. Western blotting results showed that UHRF2 overexpression significantly activated the phosphorylation of PI3K and Akt proteins in the HCC cells. Conclusion The expression of UHRF2 is closely related to the prognosis of HCC patients, and is an independent risk factor for HCC patients. Overexpression of UHRF2 promotes the proliferation and metastasis of HCC cells through the PI3K/Akt signaling pathway.