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

Gang Wu,Yawei Wang,Xiaojun Lu,Haiyang Liu,Yongfeng Liu,Shuguan Xia,Xiangyu Meng,Yanqiu Yu,Hui He

doi:10.1186/1471-2407-14-107

Abstract

BackgroundATAD2 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).MethodsThe 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.ResultsATAD2 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.ConclusionsThe 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.

Highlights

ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion
Recently Huang Q et al has reported that a novel, highly up-regulated exon-exon junction was detected in ATAD2 gene by RNA-seq and the gene was highly expressed in hepatocellular carcinoma (HCC) tissues [14]
A multivariate analysis demonstrated that ATAD2 status, the tumor size, metastasis and the AFP status were significant prognostic factors for HCC patients (Table 2)

Summary

Introduction

ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. No studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC). The long-term prognosis is still unsatisfactory, largely due to the high recurrence and invasion rates even after resection (50-70% at five years) [4,5]. The structure of ATAD2 suggests that it has functions related to genome regulation, including cell proliferation, differentiation and apoptosis. Studies have revealed that ATAD2 is highly expressed in several types of tumors such as breast cancer, lung cancer, and large B-cell lymphoma [8,9,10,11,12,13]. There have been no studies on the gene function and prognosis associated with ATAD2 in HCC

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Discussion

Conclusion