GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

Abstract

Previous studies have reported that GATA3 is downregulated in multiple types of tumours, including gastric cancer and osteosarcoma. The aim of this study was to explore whether GATA3 serves as a tumour suppressor to inhibit hepatocellular carcinoma (HCC) development. Tumour tissue specimens and adjacent normal tissue specimens were obtained from 162 patients diagnosed with HCC in the Affiliated Hospital of Shaoxing University from July 2000 to May 2018. The result of the present study demonstrated that GATA3 was downregulated in HCC tumour tissues compared with that of adjacent normal tissues. The expression of GATA3 was also negatively associated with tumour size, TNM stage and lymph node metastasis. Additionally, analysis of the follow-up data revealed that low GATA3 expression was closely correlated with poor survival. Gain and loss of function analyses revealed that overexpression of GATA3 decreased the ability of proliferation, migration and invasion in HCC cell lines, whereas inhibition of GATA3 promoted the ability of proliferation, migration and invasion. In addition, GATA3 suppressed EMT through the regulation of slug expression. Additionally, slug overexpression attenuated the inhibitory effects of GATA3 overexpression on cancer cell proliferation, migration and invasion. Thus, GATA3 is downregulated in HCC, and suppresses cell proliferation, migration and invasion. Moreover, GATA3 transcriptionally inhibits slug expression, thereby suppressing EMT in HCC.

Relationship between tumor thickness and GATA3 immunoexpression in lip and tongue squamous cell carcinomas

“…These ndings are in line with the study by Zhang et al [9] who found that higher GATA3 immunoexpression was associated with low-grade bladder cancer. Zhang et al [17] made a similar observation in a study following up patients with hepatocellular carcinoma (HCC), in which lower GATA3 expression was associated with a poor prognosis. The authors suggested that overexpression of GATA3 decreased the proliferative, migratory and invasive capacity of HCC cell lines, while inhibition of GATA3 stimulated proliferation, migration, and invasion.…”