IL-21R functions as an oncogenic factor and is regulated by the lncRNA MALAT1/miR-125a-3p axis in gastric cancer

Yan,Lei; Zhang,Jing; Guo,Dong; Ma,Ji; Shui,Shao-Feng; Han,Xin-Wei

doi:10.3892/ijo.2018.4612

IL-21R functions as an oncogenic factor and is regulated by the lncRNA MALAT1/miR-125a-3p axis in gastric cancer

Authors:
- Lei Yan
- Jing Zhang
- Dong Guo
- Ji Ma
- Shao-Feng Shui
- Xin-Wei Han
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Affiliations: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China, Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: October 31, 2018 https://doi.org/10.3892/ijo.2018.4612
Pages: 7-16
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin-21 receptor (IL-21R) is involved in the immunological regulation of immune cells and tumor progression in multiple malignancies. However, the potential molecular mechanisms through which non-coding RNAs (ncRNAs) modulate IL-21R signaling in gastric cancer (GC) remain elusive. In this study, the expression of IL-21R was detected by RT-qPCR and western blot analysis in GC cell lines. The association between IL-21R expression and clinicopathological characteristics and the prognosis of patients with GC was analyzed by immunohistochemistry and Kaplan-Meier plotter analysis. The biological functions of IL-21R were analyzed by a series of in vitro and in vivo experiments, and its regulation by ncRNAs was predicted by bioinformatics analysis and confirmed by luciferase assays and rescue experiments. As a result, the expression of IL-21R was found to be significantly increased in GC cell lines and tissues as compared with normal tissues, and was associated with tumor size and lymphatic metastasis, acting as an independent prognostic factor of poor survival and recurrence in patients with GC. The knockdown of IL-21R markedly suppressed GC cell proliferation and invasion, and IL-21R expression was further validated to be negatively regulated by miR-125a-3p (miR-125a). The overexpression of IL-21R reversed the tumor suppressive effects of miR-125a in vitro and in vivo. Moreover, lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acted as a sponge of miR-125a to modulate the IL-21R signaling pathway in GC cells and represented a risk factor for survival and recurrence in patients with GC. Taken together, the findings of this study reveal an oncogenic role for IL-21R in gastric tumorigenesis and verify that its activation is partly due to the dysregulation of the lncRNA MALAT1/miR-125a axis. These findings may provide a potential prognostic marker for patients with GC.

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