SUZ12/CXCR7 axis promotes invasion potential and is associated with portal vein tumor thrombus in hepatocellular carcinoma

Abstract

AbstractBackground Polycomb protein suppressor of zeste 12 (SUZ12) has been widely revealed involving in development and diverse physiopathology processes. However, the roles of SUZ12 in hepatocellular carcinoma (HCC) remain largely unknown. Methods Tissue microarray was used to examine the expression level of SUZ12. The gain- and loss- of function analysis were conducted to evaluate the effects of SUZ12 on the proliferation, migration and invasion of HCC cells. Meanwhile, luciferase reporter assay and RT-PCR assay were conducted to examine the effect of SUZ12 on transcriptional activity of chemokine receptors 7 (CXCR7). Results The expression level of SUZ12 was positively associated with HCC development, as revealed by tissue microarray analysis. Further gain- and loss- of function analysis demonstrated that SUZ12 promoted the proliferation, migration and invasion of HCC. Mechanistically, we found that SUZ12 could upregulate the expression of CXCR7 at the transcriptional level in HCC cells, and CXCR7 was revealed to contribute to the tumor-promoting roles of SUZ12. Of interest, luciferase reporter assay revealed SUZ12 positively controlled the CXCR7 via direct promoter combination but not epigenetic suppression. Moreover, high SUZ12 expression was positively correlated with CXCR7 in advanced patients with portal vein tumor thrombus. Conclusion Our findings indicate that SUZ12 plays pro-oncogenic roles in the progression of HCC, partially by activating CXCR7 signaling, especially in HCC patients with portal vein tumor thrombus. The SUZ12/CXCR7 axis may serve as a potential therapeutic target for treatments of advanced HCC patients.