摘　要：肝癌是肝脏中最常见的恶性肿瘤，是全球癌症相关死亡的第三大主要原因。肝癌发病具有隐蔽性、细胞异质性、耐药性的特点，且肿瘤易侵袭、转移和复发，使得其临床治疗效果欠佳。转录因子AP-2α在肝癌中作为肿瘤抑制因子发挥作用，其表达与肝癌患者的预后呈现正相关。SOX9在细胞分化、性别决定和肿瘤发生中起主要作用。在肝癌细胞中，SOX9异常增加可以促进癌细胞的生长。本研究利用JASPAR软件预测到SOX9的启动子区域含有潜在的AP-2α结合位点，通过萤光素酶和凝胶迁移试验（EMSA）证实了AP-2α可以与SOX9的启动子区域直接结合，抑制SOX9的转录活性。通过实时定量PCR和蛋白质免疫印迹发现，AP-2α抑制了SOX9的mRNA和蛋白质水平表达。这些结果提示了AP-2α可与癌基因SOX9的启动子区域结合，负调控肝癌细胞中SOX9的表达。
关键词：肝癌；AP-2α；SOX9；基因调控；转录因子
中图分类号：R735.7                                文献标志码：A                 DOI：10.3969/j.issn.1007-7146.2022.06.005

Abstract: Hepatocarcinoma is the most common malignant tumor of the liver and the third leading cause of cancer related deaths worldwide. The incidence of hepatocarcinoma is characterized by concealment, cell heterogeneity and drug resistance, and the tumor is prone to invasion, metastasis and recurrence, which makes the clinical treatment effect of hepatocarcinoma poor. Transcription factor AP-2α plays an important role as a tumor suppressor in hepatocarcinoma, whose expression is positively correlated with the prognosis of hepatocarcinoma patients. SOX9 plays a major role in cell differentiation, sex determination and tumorigenesis. The abnormal increase of SOX9 was found in liver cancer, which promoted the growth of cancer cells. In our study, we used JASPAR software analysis to predict the potential binding sites of AP-2α in the promoter region of the SOX9 gene. The potential binding site of AP-2α was confirmed by luciferase assays and electrophoretic mobility shift assay(EMSA). AP-2α can directly bind to the promoter region of the SOX9 gene and inhibit its transcription activity. We found that AP-2α suppresses the expression of SOX9 at both mRNA and protein levels by real-time quantitative PCR and Western blots. These results revealed that AP-2α binds to the promoter region of the SOX9 gene, and negatively regulates the expression of oncogene SOX9 in hepatocarcinoma cells.
Key words: liver cancer; AP-2α; SOX9; gene regulation; transcription factor
（Acta Laser Biology Sinica, 2022, 31(6): 512-517）