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OIT3 mediates macrophage polarization and facilitates hepatocellular carcinoma progression.

Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality; however, effective immunotherapy strategies are limited because of the immunosuppressive tumor microenvironment. Macrophages are essential components of the HCC microenvironment and are related to poor prognosis. Here, we evaluated the attributes of paracancer tissues in tumor immunity and progression using public databases. Based on the abundance of immune cells estimated by CIBERSORT, we performed weighted gene co-expression network analysis and found a specific module associated with M2 macrophages. Through analyzing interaction networks using Cytoscape and public datasets, we identified oncoprotein-induced transcript 3 (OIT3) as a novel marker of M2 macrophages. Overexpression of OIT3 remodeled immune features and reprogrammed the metabolism of M2 macrophages. Moreover, compared with wildtype macrophages, OIT3-overexpressing macrophages further enhanced the migration and invasion of co-cultured cancer cells. Additionally, OIT3-overexpressing macrophages promoted tumorigenesis and cancer development in vivo. Taken together, the findings demonstrate that OIT3 is a novel biomarker of alternatively activated macrophages and facilitates HCC metastasis.
AuthorsShuai Yang, Jiangang Zhang, Yanquan Xu, Jingchun Wang, Huakan Zhao, Juan Lei, Yu Zhou, Yu Chen, Lei Wu, Mingyue Zhou, Lu Zheng, Xiaohui Ji, Yongsheng Li
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 71 Issue 11 Pg. 2677-2689 (Nov 2022) ISSN: 1432-0851 [Electronic] Germany
PMID35353239 (Publication Type: Journal Article)
Copyright© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Chemical References
  • Biomarkers
  • Membrane Proteins
  • OIT3 protein, human
  • Oncogene Proteins
Topics
  • Biomarkers (metabolism)
  • Carcinoma, Hepatocellular (pathology)
  • Cell Line, Tumor
  • Humans
  • Liver Neoplasms (pathology)
  • Macrophages
  • Membrane Proteins
  • Oncogene Proteins (metabolism)
  • Tumor Microenvironment

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