Knockdown of HMGN5 increases the chemosensitivity of human urothelial bladder cancer cells to cisplatin by targeting PI3K/Akt signaling

Gan,Yu; He,Leye; Yao,Kun; Tan,Jing; Zeng,Qing; Dai,Yingbo; Liu,Jianye; Tang,Yuxin

doi:10.3892/ol.2017.7045

Knockdown of HMGN5 increases the chemosensitivity of human urothelial bladder cancer cells to cisplatin by targeting PI3K/Akt signaling

Authors:
- Yu Gan
- Leye He
- Kun Yao
- Jing Tan
- Qing Zeng
- Yingbo Dai
- Jianye Liu
- Yuxin Tang
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Affiliations: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 25, 2017 https://doi.org/10.3892/ol.2017.7045
Pages: 6463-6470
Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High‑mobility group nucleosome‑binding domain 5 (HMGN5) is the latest member of the HMGN family of proteins. Numerous studies have confirmed the carcinogenic role of HMGN5 in cancer, but its function in the regulation of chemosensitivity is largely unknown and controversial. A previous study by the authors of the present study demonstrated that HMGN5 contributes to the progression of urothelial bladder cancer (UBC) through regulating the expression of E‑cadherin and vascular endothelial growth factor (VEGF)‑C, which are associated with the sensitivity of tumor cells to cisplatin. Therefore, the present study aimed to elucidate the mechanisms underlying the regulation of HMGN5 and investigate the involvement of HMGN5 in cisplatin treatment. The results of the present study revealed that HMGN5 is able to positively regulate the expression of phosphorylated (p‑)Akt in UBC cells. In addition, HMGN5 expression was negatively associated with the response of UBC cells to cisplatin. The findings indicated that HMGN5 may be a potential therapeutic target of cisplatin treatment, since cisplatin treatment reduced HMGN5 expression in a dose‑dependent manner. It was also confirmed that the knockdown of HMGN5 decreased the viability, colony formation and invasion of 5637 cells but increased apoptosis under cisplatin treatment. The changes caused by HMGN5 knockdown in 5637 cells were able to be reversed by treatment with insulin‑like growth factor‑1 (IGF‑1), which is a phosphoinositide 3‑kinase (PI3K)/Akt signaling activator. Additionally, with the decreased expression of HMGN5, the expression of p‑Akt, slug, E‑cadherin and VEGF‑C was subsequently inhibited. By contrast, the expression of cytochrome c, cleaved‑caspase‑3 and cleaved‑poly ADP ribose polymerase was increased following HMGN5 knockdown. Consistently, these changes in protein expression were able to be reversed by IGF‑1 treatment. In conclusion, findings from the in vitro experiments indicate that HMGN5 may a target of cisplatin treatment and that the inhibition of HMGN5 increases the chemosensitivity of UBC cells by inhibiting PI3K/Akt signaling.

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