Overexpression of IC53d promotes the proliferation of gastric cancer cells by activating the AKT/GSK3β/cyclin D1 signaling pathway

Lin,Jian‑Xian; Xie,Xin‑Sheng; Weng,Xiong‑Feng; Qiu,Sheng‑Liang; Xie,Jian‑Wei; Wang,Jia‑Bin; Lu,Jun; Chen,Qi‑Yue; Cao,Long‑Long; Lin,Mi; Tu,Ru‑Hong; Li,Ping; Huang,Chang‑Ming; Zheng,Chao‑Hui

doi:10.3892/or.2019.7042

Overexpression of IC53d promotes the proliferation of gastric cancer cells by activating the AKT/GSK3β/cyclin D1 signaling pathway

Authors:
- Jian‑Xian Lin
- Xin‑Sheng Xie
- Xiong‑Feng Weng
- Sheng‑Liang Qiu
- Jian‑Wei Xie
- Jia‑Bin Wang
- Jun Lu
- Qi‑Yue Chen
- Long‑Long Cao
- Mi Lin
- Ru‑Hong Tu
- Ping Li
- Chang‑Ming Huang
- Chao‑Hui Zheng
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Affiliations: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: March 5, 2019 https://doi.org/10.3892/or.2019.7042
Pages: 2739-2752
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cyclin‑dependent kinase 5 regulatory subunit‑associated protein 3 (CDK5RAP3 or C53) is involved in the development of various types of tumor, and alternative splicing of C53 results in numerous transcription variants that encode different isoforms. The present study aimed to clone human C53 isoform d (IC53d) and explore its role in the proliferation of gastric cancer cells. Reverse transcription‑quantitative polymerase chain reaction was used to detect the expression levels of IC53d in 80 primary gastric adenocarcinoma tissues and adjacent normal tissues. In addition, the association between IC53d and clinicopathological parameters was determined. Gastric cancer cell lines stably overexpressing IC53d were established to observe its effects on cell proliferation, invasion and migration, and on in vivo tumorigenicity, and the mechanism of action was explored. The results of the presen study demonstrated that IC53d was upregulated in gastric cancer tissues and was associated with tumor T‑stage. Furthermore, overexpression of IC53d promoted the proliferation, colony formation and G1/S phase transition of gastric cancer cells, leading to enhancement of tumorigenesis in vitro and in vivo. Overexpression of IC53d also promoted phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3β (GSK3β), which increased the expression of cyclin D1. In addition, high cyclin D1 expression was associated with a significantly worse prognosis for patients compared with in patients with low cyclin D1 expression. These results indicated that IC53d may promote the phosphorylation of AKT and GSK3β, which in turn may increase cyclin D1 expression, enhancing G1/S phase transition, accelerating cell cycle progression, promoting the proliferation of gastric cancer cells, and inducing a poor prognosis in patients with gastric cancer.

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