IL-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling

Background: Interleukin-37 b(IL-37 b), 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-37 b and hepatocellular carcinoma(HCC). The present study aimed to investigate the potential roles of IL-37 b in HCC progression. Methods: Subjects( n = 237) were recruited, and serum IL-37 b was measured using ELISA. The tumorsuppressive capacity and underlying mechanisms of IL-37 b in HCC were investigated in vitro and in vivo. Results: Compared to healthy controls, serum IL-37 b 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-37 b 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-37 b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37 b 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-37 b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37 b may be a biomarker for HBV-HCC and its staging.

Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway

Background:Transcription factor 3(TCF3)plays pivotal roles in embryonic development,stem cell maintenance and carcinogenesis.However,its role in hepatocellular carcinoma(HCC)remains largely unknown.This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC,and further explore the underlying mechanism in HCC progression.Methods:The expression of TCF3 was collected from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)HCC datasets,and further confirmed by immunostaining and Western blotting assays.The correlation between TCF3 expression and the clinicopathological features was evaluated.Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development.Results:Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues(P<0.001 and P<0.01).Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade,and patients with high TCF3 expression had shorter overall survival(P=0.012),disease-specific survival(P=0.022)and progression-free survival(P=0.013).Similarly,the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size(P=0.001)and TNM stage(P=0.002),and TCF3 was an independent risk factor of HCC.In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation,and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways.Conclusions:TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage,as well as poor prognosis of HCC patients.The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

Reduced-right posterior sector salvage liver transplantation using a moderate steatotic graft from one obese donor after cardiac death

To the Editor:Compared with the majority of reduced-size liver transplantations(RSLTs)performed in pediatric recipients,[1-3]the experience of RSLTs in adult recipients and surgical strategies for the reduction of grafts are relatively unfamiliar.Herein,we report a successful case of adult-to-adult RSLT,in which a unique method for removing the right posterior sector while preserving the right hepatic vein(RHV)was performed.This study was approved by the West China Hospital Ethics Committee(No.2019-718)and was conducted in accordance with the ethical guidelines of the Declaration of Helsinki.