Abstract
BackgroundThe abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear.MethodsWe used UALCAN, ONCOMINE, Kaplan–Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC.ResultsATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients.ConclusionsUsing data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.
Highlights
The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper family of transcription factors, is associated with carcinogenesis
The results revealed that ATF3 expression was lower in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), kidney chromophobe (KICH), and liver hepatocellular carcinoma (LIHC) cancer patients (Additional file 1: Fig. 1)
We detected the expression of ATF3 in hepatocellular carcinoma (HCC) cell lines, and results showed that ATF3 was significantly down-regulated in HCC cell lines compared to normal human hepatocyte (Fig. 1g)
Summary
The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. The expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. ATF3 has been shown to promote or suppress apoptosis and cell proliferation, which are critical processes for cancer progression [6]. ATF3 increases apoptosis in the untransformed mammary epithelial cell line (MCF10A). These studies clearly indicate the dual functions of ATF3 in both oncogenesis and tumor suppression [12]. It has been reported that low levels of ATF3 may suppress hepatocellular oncogenesis [14]. These results reveal that ATF3 is a novel tumor suppressor gene in HCC
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