HMGA2 promotes the migration and invasion of gallbladder cancer cells and HMGA2 knockdown inhibits angiogenesis via targeting VEGFA

Yan,Jun; Dai,Peng; Qin,Xueliang; He,Yanping; Zhang,Yu

doi:10.3892/mmr.2021.12570

HMGA2 promotes the migration and invasion of gallbladder cancer cells and HMGA2 knockdown inhibits angiogenesis via targeting VEGFA

Authors:
- Jun Yan
- Peng Dai
- Xueliang Qin
- Yanping He
- Yu Zhang
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Affiliations: Department of General Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China
Published online on: December 15, 2021 https://doi.org/10.3892/mmr.2021.12570
Article Number: 54
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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