Department of General Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China.
Mol Med Rep. 2022 Feb;25(2). doi: 10.3892/mmr.2021.12570. Epub 2021 Dec 16.
The high mobility group AT‑hook 2 (HMGA2) protein has been found to be upregulated in the majority of tumor types and is associated with a poor prognosis. Previous studies have suggested the oncogenic role of HMGA2 in gallbladder cancer (GBC). The present study aimed to investigate the effects of HMGA2 on the invasion, migration and angiogenesis of GBC cells. To achieve this aim, HMGA2 was overexpressed or silenced in the GBC cell line, EH‑GB1, and then the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) abilities of EH‑GB1 cells were investigated using Cell Counting Kit‑8, wound healing, Transwell and western blotting assays. In addition, the expression levels of VEGFA were determined in EH‑GB1 cells using western blotting and reverse transcription‑quantitative PCR following HMGA2 overexpression or silencing. Furthermore, HMGA2‑silenced EH‑GB1 cells were transfected with VEGFA overexpression plasmids to evaluate the tube formation ability of HUVECs using tube formation assay. The results demonstrated that HMGA2 silencing inhibited GBC cell proliferation, migration, invasion and EMT, as evidenced by the downregulated expression of Ki67, proliferating cell nuclear antigen, MMP2, MMP9, N‑cadherin, snail family transcriptional repressor 2 and zinc finger E‑box‑binding homeobox 1, and attenuated cell migration and invasion. However, the opposite results were obtained following HMGA2 overexpression. Moreover, HMGA2 knockdown and overexpression downregulated and upregulated VEGFA expression, respectively. In addition, the tube formation ability of HUVECs and the expression levels of CD31, VEGFR1 and VEGFR2 were downregulated following HMGA2 silencing. However, these effects were partially rescued by simultaneous VEGFA overexpression. In conclusion, the findings of the present study revealed that HMGA2 may promote GBC cell migration, invasion, EMT and angiogenesis. Therefore, inhibiting HMGA2 expression could be considered as a possible therapeutic approach for GBC.
高迁移率族 AT 钩 2（HMGA2）蛋白在大多数肿瘤类型中上调，与预后不良相关。先前的研究表明 HMGA2 在胆囊癌（GBC）中具有致癌作用。本研究旨在探讨 HMGA2 对 GBC 细胞侵袭、迁移和血管生成的影响。为了达到这个目的，在 GBC 细胞系 EH-GB1 中过表达或沉默 HMGA2，然后使用细胞计数试剂盒-8、划痕愈合、Transwell 和 Western blot 测定法研究 EH-GB1 细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT）能力。此外，在过表达或沉默 HMGA2 后，使用 Western blot 和逆转录-定量 PCR 测定 EH-GB1 细胞中 VEGFA 的表达水平。此外，用 VEGFA 过表达质粒转染 HMGA2 沉默的 EH-GB1 细胞，使用管形成测定法评估 HUVECs 的管形成能力。结果表明，HMGA2 沉默抑制 GBC 细胞增殖、迁移、侵袭和 EMT，表现为 Ki67、增殖细胞核抗原、MMP2、MMP9、N-钙粘蛋白、snail 家族转录抑制因子 2 和锌指 E-框结合同源盒 1 的表达下调，并减弱细胞迁移和侵袭。然而，HMGA2 过表达时得到了相反的结果。此外，HMGA2 敲低和过表达分别下调和上调 VEGFA 表达。此外，HMGA2 沉默后，HUVECs 的管形成能力以及 CD31、VEGFR1 和 VEGFR2 的表达水平下调。然而，同时过表达 VEGFA 部分挽救了这些效应。总之，本研究的结果表明，HMGA2 可能促进 GBC 细胞迁移、侵袭、EMT 和血管生成。因此，抑制 HMGA2 表达可能被认为是治疗 GBC 的一种可能方法。
