Open Access Highly Accessed Research article

miR-372 down-regulates the oncogene ATAD2 to influence hepatocellular carcinoma proliferation and metastasis

Gang Wu1*, Haiyang Liu1, Hui He1, Yawei Wang1, Xiaojun Lu1, Yanqiu Yu2, Shuguan Xia1, Xiangyu Meng1 and Yongfeng Liu1

Author Affiliations

1 Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China

2 Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, China

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BMC Cancer 2014, 14:107  doi:10.1186/1471-2407-14-107

Published: 19 February 2014



ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. However, no studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC).


The protein and mRNA level expression of ATAD2 was examined in tissues and cell lines. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. ATAD2 knockdown was used to analyze cell proliferation and invasion. The upstream and downstream of ATAD2 was analyzed by RT2 Profiler™ PCR array and luciferasex fluorescence system.


ATAD2 was highly expressed in liver cancer samples and correlated with poor survival. High ATAD2 expression was positively correlated with metastasis (P = 0.005) and was an independent prognostic factor in HCC (P = 0.001). ATAD2 depletion by RNA interference reduced their capacity for invasion and proliferation and led to a G1 phase arrest in vitro. Further study revealed that miR-372 was an upstream target of ATAD2 as miR-372 was bound directly to its 3′ untranslated region (3′ UTR). In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.


The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis. In conclusion, ATAD2 may promote HCC progression.