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Open AccessArticle

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

1
Department of Biological Science, Gachon University, Seongnam 13120, Korea
2
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
3
Division of Biotechnology, Chonbuk National University, Iksan 54596, Korea
4
Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, Korea
5
Department of Pathology, Chonbuk National University Medical School, Chonbuk National University, Jeonju 54896, Korea
6
Research Institute of Clinical Medicine, Chonbuk National University, Jeonju 54896, Korea
7
Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Hospital, Jeonju 54896, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(9), 1394; https://doi.org/10.3390/cancers11091394
Received: 2 September 2019 / Revised: 13 September 2019 / Accepted: 15 September 2019 / Published: 18 September 2019
(This article belongs to the Special Issue Renal Cell Carcinoma)
Specific kinds of interleukin (IL) receptors are known to mediate lymphocyte proliferation and survival. However, recent reports have suggested that the high expression of IL4Rα and IL13Rα1 in tumor tissue might be associated with tumorigenesis in several kinds of tumor. We found that a significant association between mRNA level of IL4Rα or IL13Rα1 and the poor prognosis of renal cell carcinoma (RCC) from the public database (http://www.oncolnc.org/). Then, we evaluated the clinicopathological significance of the immunohistochemical expression of IL4Rα and IL13Rα1 in 199 clear cell RCC (CCRCC) patients. The individual and co-expression patterns of IL4Rα and IL13Rα1 were significantly associated with cancer-specific survival (CSS) and relapse-free survival (RFS) in univariate analysis. Multivariate analysis indicated IL4Rα-positivity and co-expression of IL4Rα and IL13Rα1 as the independent indicators of shorter CSS and RFS of CCRCC patients. For the in vitro evaluation of the oncogenic role of IL4Rα and IL13Rα1 in RCC, we knock-downed IL4Rα or IL13Rα1 and observed that the cell proliferation rate was decreased, and the apoptosis rate was increased in A498 and ACHN cells. Furthermore, we examined the possible role of Janus kinase 2 (JAK2), well-known down-stream tyrosine kinase under the heterodimeric receptor complex of IL4Rα and IL13Rα1. Interestingly, JAK2 interacted with Forkhead box O3 (FOXO3) to cause tyrosine-phosphorylation of FOXO3. Silencing IL4Rα or JAK2 in A498 and ACHN cells reduced the interaction between JAK2 and FOXO3. Moreover, pharmacological inhibition of JAK2 induced the nuclear localization of FOXO3, leading to increase apoptosis and decrease cell proliferation rate in A498 and ACHN cells. Taken together, these results suggest that IL4Rα and IL13Rα1 might be involved in the progression of RCC through JAK2/FOXO3 pathway, and their expression might be used as the novel prognostic factor and therapeutic target for RCC patients. View Full-Text
Keywords: IL4Rα; IL13Rα1; renal cell carcinoma; JAK2; FOXO3 IL4Rα; IL13Rα1; renal cell carcinoma; JAK2; FOXO3
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MDPI and ACS Style

Kang, M.-A.; Lee, J.; Ha, S.H.; Lee, C.M.; Kim, K.M.; Jang, K.Y.; Park, S.-H. Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways. Cancers 2019, 11, 1394.

AMA Style

Kang M-A, Lee J, Ha SH, Lee CM, Kim KM, Jang KY, Park S-H. Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways. Cancers. 2019; 11(9):1394.

Chicago/Turabian Style

Kang, Mi-Ae; Lee, Jongsung; Ha, Sang H.; Lee, Chang M.; Kim, Kyoung M.; Jang, Kyu Y.; Park, See-Hyoung. 2019. "Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways" Cancers 11, no. 9: 1394.

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