Tan Qianxia, Cai Jingting, Peng Jingping, Hu Cui, Wu ChenChun, Liu Huining
Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Kaifu, Changsha, Hunan, 410000, People's Republic of China.
Cancer Cell Int. 2022 Jun 30;22(1):221. doi: 10.1186/s12935-022-02641-8.
Unlike other members of the VEGF family, the function of VEGF-B in tumor progression remains to be elucidated. Thus, the present study aimed to determine the function of VEGF-B in human choriocarcinoma cells by investigating its detailed effects and molecular mechanisms. VEGF-B and aryl hydrocarbon receptor (AhR) expression were evaluated by reverse transcription-quantitative PCR analysis and western blot analysis in JEG-3 cells and choriocarcinoma stem-like cells (CSLCs) and their proliferation, migration, and invasion after the transfection of short hairpin RNA VEGF-B, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; AhR agonist) treatment or StemRegenin 1 (SR1; AhR antagonist) treatment were examined by cell proliferation assay, wound healing assay and Transwell assay. In addition, luciferase reporter analysis and bioinformatics data mining were used to investigate the association between VEGF-B and AhR. Upregulation of VEGF-B and AhR expression was observed in CSLCs. Following VEGF-B knockdown or SR1 treatment, the proliferative, migratory, and invasive abilities of CSLCs were significantly decreased, contrary to the findings after TCDD treatment. It was also found that AhR enhanced VEGF-B transcriptional activity by binding to the relative promoter region. These observations indicated that VEGF-B may be an oncogene that promotes choriocarcinoma cell migration and invasion targeted by AhR. Therefore, targeting VEGF-B may provide a novel therapeutic opportunity for choriocarcinoma.
与血管内皮生长因子（VEGF）家族的其他成员不同，VEGF-B在肿瘤进展中的功能仍有待阐明。因此，本研究旨在通过研究VEGF-B的详细作用及其分子机制，确定其在人绒毛膜癌细胞中的功能。采用逆转录定量PCR分析和蛋白质免疫印迹分析评估JEG-3细胞和绒毛膜癌干细胞样细胞（CSLCs）中VEGF-B和芳烃受体（AhR）的表达，并通过细胞增殖试验、伤口愈合试验和Transwell试验检测短发夹RNA VEGF-B转染、2,3,7,8-四氯二苯并对二恶英（TCDD；AhR激动剂）处理或StemRegenin 1（SR1；AhR拮抗剂）处理后细胞的增殖、迁移和侵袭能力。此外，利用荧光素酶报告基因分析和生物信息学数据挖掘来研究VEGF-B与AhR之间的关联。在CSLCs中观察到VEGF-B和AhR表达上调。与TCDD处理后的结果相反，VEGF-B基因敲低或SR1处理后，CSLCs的增殖、迁移和侵袭能力显著降低。还发现AhR通过与相关启动子区域结合增强VEGF-B的转录活性。这些观察结果表明，VEGF-B可能是一种促进绒毛膜癌细胞迁移和侵袭的癌基因，而AhR是其作用靶点。因此，靶向VEGF-B可能为绒毛膜癌提供一种新的治疗机会。
