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HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway

  • Authors:
    • Bo Kou
    • Wei Liu
    • Xiaoshuang Tang
    • Qingshan Kou
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Medical Center, First People's Hospital of Xianyang, Xianyang, Shaanxi 712000, P.R. China
    Copyright: © Kou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 101-108
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    Published online on: November 10, 2017
       https://doi.org/10.3892/or.2017.6091
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Abstract

High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, has been reported to correlate with cancer progression. However, there is no report concerning the correlation between HMGA2 and metastasis in renal cell carcinoma. In the present study, we found that HMGA2 was highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line. Additionally, HMGA2 facilitated cell migration and invasion of renal cell carcinoma cells, as evidenced by wound healing and Transwell assays. Subsequently, our results revealed that the E‑cadherin level was upregulated, while N‑cadherin, Twist1 and Twist2 expression were downregulated in HMGA2-depleted ACHN cells. In contrast, overexpression of HMGA2 in 786‑O cells enhanced epithelial-mesenchymal transition (EMT). In addition, analysis of the database Cancer Browser further validated the positive correlation between HGMA2 and Twist1 or Twist2 in renal cell carcinoma. Meanwhile, Kaplan-Meier analysis indicated that low HMGA2 expression was closely associated with an increased overall survival in renal cell carcinoma patients. To confirm the underlying mechanism of HMGA2-regulated EMT, our results revealed that silencing of HMGA2 downregulated the mRNA and protein levels of TGF-β and Smad2, while HMGA2 overexpression had the opposite effect. Furthermore, TGF-β overexpression could partially reverse the anti-metastatic effect and mesenchymal-epithelial transition (MET) by HMGA2 loss, while TGF-β deficiency impeded the pro‑metastatic phenotype and high expression of EMT markers induced by HMGA2 overexpression. In summary, our results demonstrated that HMGA2 facilitated a metastatic phenotype and the EMT process in renal cell carcinoma cells in vitro through a TGF-β-dependent pathway. In addition, these data strongly suggest that HGMA2 may serve as a potential therapeutic target and prognostic biomarker against renal cell carcinoma in the future.
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Copy and paste a formatted citation
Spandidos Publications style
Kou B, Liu W, Tang X and Kou Q: HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway. Oncol Rep 39: 101-108, 2018.
APA
Kou, B., Liu, W., Tang, X., & Kou, Q. (2018). HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway. Oncology Reports, 39, 101-108. https://doi.org/10.3892/or.2017.6091
MLA
Kou, B., Liu, W., Tang, X., Kou, Q."HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway". Oncology Reports 39.1 (2018): 101-108.
Chicago
Kou, B., Liu, W., Tang, X., Kou, Q."HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway". Oncology Reports 39, no. 1 (2018): 101-108. https://doi.org/10.3892/or.2017.6091
Copy and paste a formatted citation
x
Spandidos Publications style
Kou B, Liu W, Tang X and Kou Q: HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway. Oncol Rep 39: 101-108, 2018.
APA
Kou, B., Liu, W., Tang, X., & Kou, Q. (2018). HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway. Oncology Reports, 39, 101-108. https://doi.org/10.3892/or.2017.6091
MLA
Kou, B., Liu, W., Tang, X., Kou, Q."HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway". Oncology Reports 39.1 (2018): 101-108.
Chicago
Kou, B., Liu, W., Tang, X., Kou, Q."HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway". Oncology Reports 39, no. 1 (2018): 101-108. https://doi.org/10.3892/or.2017.6091
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