Comprehensive analysis of the correlations of S100B with hypoxia response and immune infiltration in hepatocellular carcinoma

PeerJ

article

Jia Yan¹  Ya jun Huang²  Qing yu Huang²  Peng Xia Liu²  Chang Shan Wang¹ 

[1] Department of Bioscience, State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University;Department of Bioscience, Inner Mongolia University

关键词: Hepatocellular carcinoma;    S100B;    Hypoxia;    HIF-1α;    Immune infiltration;   

DOI  :  10.7717/peerj.13201

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

S100B has been found to be dysregulated in many cancers including hepatocellular carcinoma (HCC). However, the functions of S100B and its underlying mechanisms in HCC remain poorly understood, especially in the tumor microenvironment. In this study, functions enrichment analysis indicated that S100B expression was correlated with hypoxia and immune responses. We found that hypoxia could induce S100B expression in an HIF-1α-dependent manner in HepG2 cells. Luciferase reporter and ChIP-qRCR assays demonstrated that HIF-1α regulates S100B transcription by directly binding to hypoxia-response elements (HREs) of the S100B promoter. Functionally, knockdown of S100B reduces hypoxia-induced HepG2 cell invasion and migration. Furthermore, GSVA enrichment results displayed that S100B and its co-expressed genes were positively correlated with EMT pathway in HCC. Additionally, GO/KEGG cluster analysis results indicated that co-expressed genes of S100B were involved in biological processes of immune response and multiple tumor immune-related signaling pathways in HCC. S100B expression was positively correlated with multiple immune cells tumor infiltration and associated with chemokines/chemokine receptors and immune checkpoint genes. Moreover, S100B is predominantly expressed in immune cells, especially NK (Natural Killer) cell. In addition, the hub genes of S100B co-expression and hypoxia response in HepG2 cell were also associated with immune cells infiltration in HCC. Taken together, these findings provide a new insight into the complex networks between hypoxia response and immune cells infiltration in tumor microenvironment of liver cancer. S100B maybe serve as a novel target for future HCC therapies.

【 授权许可】

CC BY