title: Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.
abstract: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1β. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1β, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1β. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Sen
authors: S
authors: Wang
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Weifang
authors: W
authors: An
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Yunhong
authors: Y
authors: Yao
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Renhuai
authors: R
authors: Chen
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China; ; 2. Clinical Laboratory, Guanghua hospital, Dongguan 523808, China;
authors: Xiaoxuan
authors: X
authors: Zheng
authors: 2. Clinical Laboratory, Guanghua hospital, Dongguan 523808, China;
authors: Wanyong
authors: W
authors: Yang
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Yi
authors: Y
authors: Zhao
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Xinrong
authors: X
authors: Hu
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Enping
authors: E
authors: Jiang
authors: 3. Pathology, People's Hospital of Xiaolan, Zhongshan 528415, China.
authors: Yanhong
authors: Y
authors: Bie
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Zhangquan
authors: Z
authors: Chen
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Ping
authors: P
authors: Ouyang
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: He
authors: H
authors: Zhang
authors: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;
authors: Hui
authors: H
authors: Xiong
keywords: Cervical cancer; Interleukin 37; Invasion.; Proliferation