title: An ANCCA/PRO2000-miR-520a-E2F2 regulatory loop as a driving force for the development of hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: T
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California at Davis Cancer Center, Davis, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangdong, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo