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Interleukin-38 Suppresses Cell Migration and Proliferation and Promotes Apoptosis of Colorectal Cancer Cell Through
Lifeng Huang1, Hongmei Zhang1, Dan Zhao1
1Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Inflammatory cytokines has been of great interest in the field of colorectal cancer (CRC) tumor immunology in recent years. As an anti-inflammatory interleukin (IL), IL-38 may contribute to the early diagnosis of CRC and improve the prognosis of CRC patients. This study was designed to investigate the role of circulating IL-38 and the regulatory mechanism of IL-38 in CRC. Expression of IL-38 were detected by ELISA and immunohistochemical staining. The influence of IL-38 on CRC were evaluated by Western blot and cell biology assays after CRC cells were treated by rhIL-38 or LM22B-10. We also verified the anti-tumor activity of IL-38 in transgenic mouse model. The expression of IL-38 was found to be correlated with progression of CRC. IL-38 inhibits CRC metastasis, proliferation and facilitates apoptosis through suppressing the activation of extracellular signal-regulated kinases (ERK) signaling pathway inducing the decrease of downstream genes, which were partially abrogated by ERK activator LM22B-10 in vitro. We also found that IL-38 overexpression inhibits tumorigenesis in vivo. Our findings indicate that IL-38 may serve as a serum prediction marker to identify the prognosis of CRC patients. IL-38 may inhibit the progression of CRC by negatively regulation on ERK signaling pathway.
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