The regulation of cytokine signaling by retinal determination gene network pathway in cancer

Xinhua Zheng,1,2,* Qian Liu,2,* Ming Yi,2 Shuang Qin,2 Kongming Wu2 1Department of Clinical Medicine, Medical School of Pingdingshan University, Pingdingshan, Henan 467000, China; 2Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China *These authors contributed equally to this work Abstract: Tumor environment plays a pivotal role in determining cancer biology characteristics. Cytokine factors, as a critical component in tumor milieu, execute distinct functions in the process of tumorigenesis and progression via the autocrine or paracrine manner. The retinal determination gene network (RDGN), which mainly comprised DACH, SIX, and EYA family members, is required for the organ development in mammalian species. While the aberrant expression of RDGN is involved in the proliferation, apoptosis, angiogenesis, and metastasis of tumors via interacting with different cytokine-related signals, such as CXCL8, IL-6, TGF-β, FGF, and VEGF, in a cell- or tissue-dependent manner. Thus, joint detection of this pathway might be used as a potential biomarker for the stratification of target therapy and for the precision prediction of the prognosis of cancer patients. Keywords: DACH1, SIX1, EYA1, cytokine, tumor, proliferation, metastasis