IL-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling
Xing-Yu Pu a , Dao-Feng Zheng b , Ai Shen c , Hai-Tao Gu d , Xu-Fu Wei b , Tong Mou b , Jian-Bo Zhang d , Rui Liu d , ∗
a Department of Medical Imaging, Chongqing Medical University, Chongqing 400016, China b Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China c Department of Hepatobiliary Surgery, Chongqing Cancer Institute, Chongqing 400030, China d Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
∗ Corresponding author.
E-mail address: lrcool@hospital.cqmu.edu.cn (R. Liu).
Interleukin-37b (IL-37b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between IL-37b and hepatocellular carcinoma (HCC). The present study aimed to investigate the potential roles of IL-37b in HCC progression.
METHODS:
Subjects (n?=?237) were recruited, and serum IL-37b was measured using ELISA. The tumor-suppressive capacity and underlying mechanisms of IL-37b in HCC were investigated in vitro and in vivo.
RESULTS:
Compared to healthy controls, serum IL-37b levels were elevated in chronic hepatitis B (CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum IL-37b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human IL-37b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating IL-6, pSTAT3 (Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human IL-6.
CONCLUSIONS:
IL-37b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37b may be a biomarker for HBV-HCC and its staging.
2018, Vol. 17 
