Cancer Management and Research (Aug 2023)
The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC
Abstract
Yanmei Song,* Huiyuan Chu,* Fang Liu, Wenjie Guo, Na Gao, Che Chen, Shisan Bao Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Che Chen; Shisan Bao, Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, 35, Dingxi East Road, Chengguan, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 187 09312856 ; +81 180 176 84959, Email [email protected]; [email protected]: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer.Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro.Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis.Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.Keywords: hepatocellular carcinoma, interleukin-36α, prognosis, biomarker
