TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Wang,Xin‑Hong; Chen,Zhi‑Guo; Xu,Rui‑Ling; Lv,Cheng‑Qian; Liu,Jing; Du,Bing

doi:10.3892/ol.2017.5814

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Authors:
- Xin‑Hong Wang
- Zhi‑Guo Chen
- Rui‑Ling Xu
- Cheng‑Qian Lv
- Jing Liu
- Bing Du
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Center of Educational Technology and Information, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Published online on: March 6, 2017 https://doi.org/10.3892/ol.2017.5814
Pages: 3239-3246

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Abstract

The transforming growth factor-β (TGF-β) signaling pathway serves a key role in the pathogenesis of liver cancer. To investigate the association between TGF‑β1 and the following proteins: Proliferating cell nuclear antigen (PCNA), gankyrin, general vesicular transport factor p115 (p115), X‑linked inhibitor of apoptosis protein (XIAP) and survivin, HepG2 liver cancer cells were transfected with small interfering RNA (siRNA) directed against TGF‑β1, or were treated with exogenous TGF‑β1. TGF‑β1 protein expression levels were assessed at 72 and 96 h using western blotting, cell growth was evaluated using a Cell Counting kit‑8 assay, and flow cytometry was used to examine cell cycle distribution and apoptosis. In addition, PCNA, gankyrin, p115, XIAP and survivin protein levels were evaluated using western blotting. TGF‑β1 protein expression levels were decreased at 72 and 96 h following siRNA transfection, indicating that the siRNA against TGF‑β1 was effective. In the TGF‑β1‑knockdown group, the HepG2 cells exhibited G1 or S‑phase cell cycle arrest; therefore, the number of G2‑phase cells was decreased, cell growth was inhibited and apoptotic peaks were observed. By contrast, no significant alteration in cell cycle distribution or apoptosis was observed in the cells treated with exogenous TGF‑β1. In the exogenous TGF‑β1 group, PCNA and XIAP protein expression levels were increased, whereas gankyrin, p115 and survivin protein expression was observed to be dependent on the duration of treatment. By contrast, PCNA, gankyrin, XIAP and survivin protein expression decreased following TGF‑β1 knockdown; however, p115 protein expression increased. In conclusion, the TGF‑β1 signaling pathway may affect cell growth, cell cycle distribution and apoptosis through the regulation of PCNA, gankyrin, p115, XIAP and survivin protein expression in liver cancer. The results of the present study may improve the current understanding of the role of the TGF-β signaling pathway during the pathogenesis of liver cancer.

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