Tnfrsf12a

What is TNFRSF12A protein?

TNFRSF12A gene (TNF receptor superfamily member 12A) is a protein coding gene which situated on the short arm of chromosome 16 at locus 16p13. TNFRSF12A, also known as CD266 or Fn14, is a member of the tumor necrosis factor receptor superfamily, a cell surface receptor that is primarily expressed on a variety of cell types, including certain immune cells, liver cells, and tumor cells. TNFRSF12A plays a role in a variety of biological processes, including cell proliferation, differentiation, migration, and cell death, particularly in tumor development, liver disease, and heart disease. The TNFRSF12A protein is consisted of 129 amino acids and TNFRSF12A molecular weight is approximately 13.9 kDa.

What is the function of TNFRSF12A protein?

TNFRSF12A is a cell surface receptor that belongs to the tumor necrosis factor receptor superfamily. It plays a role in regulating cell proliferation, differentiation, migration and death, and is particularly closely associated with tumor development, liver disease and heart disease. TNFRSF12A is involved in tumor cell invasion and metastasis by activating multiple cell signaling pathways, such as the NF-κB and MAPK families, as well as pyrodeath of hepatocytes in cirrhosis and liver injury. In addition, it plays a role in the development of heart enlargement and heart failure. Expression levels of TNFRSF12A are associated with poor prognosis in a variety of cancers, making it a potential therapeutic target.

Fig1. TWEAK/Fn14 axis in cardiovascular disease. (Nerea Méndez-Barbero, 2020)

TNFRSF12A related signaling pathway

TNFRSF12A protein is involved in a variety of cellular processes including cell proliferation, differentiation, migration and apoptosis. TNFRSF12A is particularly important in tumor development, liver disease and heart disease. In terms of signaling, TNFRSF12A activates several key events related to tumor inflammation, angiogenesis, and epithelial-stromal transformation (EMT). It can trigger downstream signals to regulate a variety of intracellular signaling pathways including NF-κB, ERK, JNK, FAK, etc. Expression levels of TNFRSF12A are associated with poor prognosis in a variety of cancers, making it a potential therapeutic target. In addition, TNFRSF12A also plays a role in the regulation of hepatocyte pyroptosis in cholestasis, and is involved in the cell death process through the NFκB/Caspase-1/GSDMD signaling pathway.

TNFRSF12A related diseases

TNFRSF12A protein is associated with a variety of diseases, especially the occurrence and development of tumors. It plays a role in the proliferation, migration and invasion of tumor cells, and its expression level correlates with tumor invasiveness, metastasis and therapeutic response, making it a potential target for tumor therapy. In addition to tumors, TNFRSF12A is also implicated in liver diseases, such as biliary atresia, where activation of the TNFRSF12A signaling pathway promotes pathological responses of bile duct cells. In addition, TNFRSF12A has a role in heart disease, for example in regulating left ventricular hypertrophy. In liver disease, TNFRSF12A promotes pyrodeath of hepatocytes through the NFκB/Caspase-1/GSDMD signaling pathway. Therefore, TNFRSF12A plays a key role in multiple pathological processes and is an important research object for future treatment strategies.

Bioapplications of TNFRSF12A

TNFRSF12A plays an important role in the proliferation, migration, invasion and metastasis of tumor cells, and its expression level is correlated with tumor prognosis. TNFRSF12A has potential applications in tumor immunotherapy, vaccine development, and as a biomarker. In addition, TNFRSF12A also plays a role in liver disease, such as promoting bile acid-induced pyroptosis of hepatocytes, which plays a key role in cirrhosis and liver injury. The study found that the increased expression of TNFRSF12A is associated with hepatocyte pyrodeath and liver injury, providing a new potential target for the treatment of liver disease.

Case Study 1: Tao Wang, 2017

In a study on human liver cancer (HCC), which is typically resistant to standard chemotherapy, researchers used microarray technology to find genes that are expressed differently in HCC compared to normal tissue. They identified 22 such genes, with TNFRSF12A being significantly overexpressed in cancerous tissue. Since TNFRSF12A is linked to cancer progression, they used siRNA to reduce its expression in liver cancer cells, which resulted in decreased cell growth and metastasis. These findings indicate that TNFRSF12A could be a potential target for HCC treatment, and other differentially expressed genes warrant further investigation.

Fig1. TNFRSF12A expression detected in SMMC7721 cells following different siRNA transfection through western blotting.

Fig2. Quantitative differences of cells between NC and si-TNFRSF12A transfection following transfection of different siRNAs and incubation.

Case Study 2: Timothy G Whitsett, 2012

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often characterized by mutations in the EGFR gene that lead to receptor activation and sensitivity to EGFR tyrosine kinase inhibitors (TKIs). This study found that NSCLC tumors frequently overexpress fibroblast growth factor-inducible 14 (Fn14, also known as TNFRSF12A), which correlates with phosphorylated EGFR (p-EGFR) levels. NSCLC cell lines with EGFR-activating mutations exhibit high Fn14 expression, and this expression is reduced by EGFR TKI treatment in EGFR-mutant HCC827 cells. Conversely, EGF stimulation increases Fn14 expression in EGFR wild-type A549 cells. Notably, Fn14 is highly expressed in EGFR-mutant H1975 cells that have developed resistance to TKIs. Experiments show that Fn14 knockdown decreases cell migration and invasion in vitro, while overexpression enhances these processes and increases lung metastases in vivo.

Fig3. Fn14 expression levels in various NSCLC cell lines.

Fig4. Transwell migration assay of A549 cells expressing control or Fn14 shRNA and either left untreated or treated with 50 ng/mL EGF.

Tnfrsf12a has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Tnfrsf12a itself. We selected most functions Tnfrsf12a had, and list some proteins which have the same functions with Tnfrsf12a. You can find most of the proteins on our site.

Tnfrsf12a has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Tnfrsf12a here. Most of them are supplied by our site. Hope this information will be useful for your research of Tnfrsf12a.

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