An ANCCA/PRO2000-miR-520a-E2F2 regulatory loop as a driving force for the development of hepatocellular carcinoma

作者：Huang, J.; Yang, J.; Lei, Y.; Gao, H.; Wei, T.; Luo, L.; Zhang, F.; Chen, H.; Zeng, Q.; Guo, L.^*

来源：Oncogenesis, 2016, 5(5): e229.

DOI：10.1038/oncsis.2016.22

• PROTEIN
• PROLIFERATION
• ANCCA
• E2F
• COACTIVATOR
• PROSTATE
• PATHWAY
• ROLES
• ATAD2
• GAP

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia especially in China. We previously identified that ANCCA/PRO2000 as an important proliferation-associated protein predicted poor prognosis of patients with HCC. However, the molecular mechanisms of ANCCA/PRO2000 leading to hepatocarcinogenesis and progression are still obscure. In the present study, we found that ANCCA/PRO2000 overexpression in HCC specimens correlated with aggressive tumor behavior and poor survival. Furthermore, ANCCA/PRO2000 exerts strong oncogenic function in HCC and promotes cell proliferation by regulating E2F2 expression, a critical cell cycle regulator. Notably, miR-520a is an intermediate regulator between ANCCA/PRO2000 and E2F2. Mechanistically, ANCCA/PRO2000 not only interacts with E2F2 but also negatively regulates miR-520a that inhibits E2F2 to cooperatively promote in vitro and in vivo growth of HCC cells. Moreover, we demonstrated that ANCCA/PRO2000 enhances the migratory capacity of HCC cells partially by suppressing ERO1L and G3BP2 expression. Additional research identified that miR-372, as a prognostic factor for HCC, could directly target ANCCA/PRO2000. Our results suggest the ANCCA/PRO2000-miR-520a-E2F2 regulatory loop as a driving force for HCC development and ANCCA/PRO2000 as a potential therapeutic target for HCC.

• 出版日期2016-5
• 单位南方医科大学