Ectopic expression of E3 ubiquitin‑protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ‑light‑chain‑enhancer of B cells

Bai,Jian; Xiao,Li; Tao,Zhen; Cao,Bingzhen; Han,Yong; Fan,Wenmei; Kong,Xiangrui; Ma,Xihui; Gao,Yu; Bi,Lili; Chen,Wen; Shi,Bingyi; Liu,Xicheng

doi:10.3892/ol.2018.9153

Ectopic expression of E3 ubiquitin‑protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ‑light‑chain‑enhancer of B cells

Authors:
- Jian Bai
- Li Xiao
- Zhen Tao
- Bingzhen Cao
- Yong Han
- Wenmei Fan
- Xiangrui Kong
- Xihui Ma
- Yu Gao
- Lili Bi
- Wen Chen
- Bingyi Shi
- Xicheng Liu
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Affiliations: Institute of Organ Transplantation, The 309th Hospital of Chinese People's Liberation Army, Beijing 100091, P.R. China, Department of Neurosurgery, General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China, Experimental Animal Centre, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110032, P.R. China, Department of Anesthesia, Shenzhen People's Hospital, Shenzhen, Guangdong 5188020, P.R. China
Published online on: July 17, 2018 https://doi.org/10.3892/ol.2018.9153
Pages: 4391-4399
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nuclear factor κ‑light‑chain‑enhancer of B cells (NF‑κB) is one of the most important tumorigenic factors. Although it has been established that NF‑κB is overly activated in human glioma cells, the molecular mechanisms that lead to the signal transduction to NF‑κB and thereby the induction of resistance to apoptosis remain poorly understood. The present study demonstrated that mRNA and protein levels of E3 ubiquitin‑protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. Immunohistochemical analysis also revealed high levels of MIB2 expression in glioma specimens. Ectopic overexpression of MIB2 was established in glioma cell lines to investigate its fundamental roles in the response of human glioma to apoptotic inducers. The results indicated that ultraviolet irradiation‑induced cell apoptosis was inhibited with MIB2 overexpression in glioma cells. Notably, knockdown of MIB2 using RNA interference was able to increase the sensitivity of glioma cells to the pro‑apoptotic agents. The present study identified that MIB2 induces NF‑κB activation and facilitates the resistance of glioma cell to apoptosis. It was proposed that MIB2 may not only be an important hallmark to glioma disease progression, but that it may also offer novel clinical strategies to overcome resistance to cancer therapies.

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