Abstract
BackgroundRunt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).MethodsRUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.ResultsRUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.ConclusionRUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
Highlights
Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC)
In gastric cancer cell lines, RUNX3-induced apoptosis depends on Bim expression [22]
The results of the present study demonstrated that RUNX3 is a tumor suppressor gene for HCC
Summary
Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). Runt-related transcription factor 3 (RUNX3), located on chromosome 1p36, is correlated with tumorigenesis and gastric cancer progression [18,19]. In gastric cancer cell lines, RUNX3-induced apoptosis depends on Bim expression [22]. RUNX3 protein expression is decreased about 45-60% in human gastric cancer [21] and has been detected in some human malignancies such as those of the colon, lung, pancreas, and bile duct [23,24,25,26]. RUNX3 gene expression decreased in 30-80% of HCCs due to LOH and methylation of its promoter [27,28]. The loss or decrease of RUNX3 expression in HCC tissue has been recently reported [29], but the precise function of RUNX3 in HCC needs to be elucidated
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