THG-1/TSC22D4 promotes inflammatory IL-1/NF-κB pathway.

Malignant neoplasms arise within a region of chronic inflammation caused by tissue injuries. Inflammation is a key factor involved in all aspects of tumorigenesis including initiation, proliferation, invasion, angiogenesis, and metastasis. Interleukin-1 (IL-1) plays critical functions in tumor development with influencing the tumor microenvironment and promoting cancer progression. RNA sequencing analysis performed with HaCaT-HRasG12V cells, HaCaT-HRasG12V-THG-1 (WT) cells and HaCaT-HRasG12V THG-1 (S264A mutant) cells revealed that THG-1 overexpression enhances the transcription of NF-κB targets including IL1A, IL1B, TNFA, and IL8. A human keratinocyte HaCaT cell line was used in this study. Oncogenic HRasG12V mutant was first expressed in HaCaT cells (HaCaT-Ras). The HaCaT-Ras cells were further transduced with empty vector (-), THG-1 wild type (WT), and THG-1 (S264A). As a result, HaCaT-Ras (-), HaCaT-Ras-THG-1 (WT), and THG-1 (S264A) cell lines were generated. Total RNA was extracted from the three cell lines cultured in DMEM containing 10% fetal bovine serum.