Egr1, also known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, is a transcription factor. It can be activated by a wide range of stimuli, and functions as a convergence point for multiple signaling cascades, coupling short-term extracellular signals to transcriptional regulation. Egr1 is involved in various biological processes such as tissue injury, immune responses, fibrosis, and is closely related to the initiation and progression of cancer. It also plays a role in the development, homeostasis, and healing of connective tissues by regulating extracellular matrix-related genes [1,5,6].

In pancreatic cancer, Egr1 is highly expressed, promotes epithelial-mesenchymal transition (EMT) via the P300/SNAI2 pathway, and enhances the migration and invasion of pancreatic cancer cells, with in vivo experiments showing it promotes liver metastasis [2].

In hepatocellular carcinoma (HCC), Egr1 expression is decreased. Over-expression of Egr1 hinders HCC cell proliferation and represses xenografted tumor development by transcriptionally down-regulating PFKL, and also increases the sensitivity of HCC cells and xenografted tumors to sorafenib [3].

In acute kidney injury (AKI), Egr1 is rapidly and transiently up-regulated. Genetic inhibition of Egr1 in mouse models aggravates AKI severity. Egr1 promotes the proliferation of SOX9 + renal tubular cells by directly binding to the Sox9 gene promoter, highlighting its potential as a therapeutic target for AKI [4].

In breast cancer, Egr1 is often down-regulated, and its knockdown is positively correlated with poor survival. Over-expression of Egr1 inhibits breast cancer cell proliferation and facilitates erastin-induced ferroptosis by activating the Nrf2-HMOX1 signaling pathway [7,8].

In osteoporosis, Egr1 promotes osteoclastogenesis by mediating the METTL3/m6A/CHI3L1 axis, and its down-regulation alleviates ovariectomy-induced osteoporosis in mice [9].

In gastric cancer, Egr1 in mesothelial cells is up-regulated in peritoneal metastases, promoting the EMT and stemness phenotypes of gastric cancer cells through the EGR1/TGF-β1/CD44s/STAT3 signaling pathway [10].

In conclusion, Egr1 is a multifunctional transcription factor involved in diverse biological processes. Gene-knockout (KO) or conditional-knockout (CKO) mouse models have revealed its crucial roles in cancer, kidney injury, osteoporosis, etc. These findings help to understand the biological functions of Egr1 and provide potential therapeutic targets for related diseases.