Serpina12, also known as Vaspin (visceral adipose tissue-derived serine protease inhibitor), is a serine protease inhibitor and an adipokine. It is involved in multiple biological processes. In adipose tissue, it is associated with insulin resistance, obesity, and inflammation. Its expression is positively correlated with body mass index and insulin sensitivity, suggesting a role in whole-body energy homeostasis [2,3].

In hepatocellular carcinoma (HCC), Serpina12 is preferentially overexpressed in epithelial HCC CD133 + cells. It promotes the tumorigenic capacity of HCC stem cells through hyperactivation of the AKT/β -catenin signaling cascade. Intravenous administration of rAAV8 -shSerpina12 in an immunocompetent HCC mouse model sensitized HCC cells to sorafenib and impeded the cancer stem cell subset, indicating its potential as a therapeutic target in HCC [1]. Loss -of -function variants in Serpina12 underlie autosomal recessive palmoplantar keratoderma. Downregulation of Serpina12 in three -dimensional skin equivalents led to epidermal acanthosis and hyperkeratosis, mimicking the human phenotype. Decreased Serpina12 expression also reduced the inhibition of kallikrein 7 activity and decreased levels of desmoglein -1 and corneodesmosin, which are important for normal epidermal differentiation [4].

In conclusion, Serpina12 plays essential roles in multiple physiological and pathological processes. In disease areas such as HCC and palmoplantar keratoderma, research on Serpina12, especially through functional studies like the use of in vivo models in HCC, helps to understand its functions and provides potential directions for treatment. Its role in regulating proteolytic activity in epidermal homeostasis and promoting tumorigenesis in HCC highlights its significance in both skin -related and cancer -related research.

References:

1. Yu, Huajian, Zhou, Lei, Loong, Jane H C, Yu, Jun, Ma, Stephanie. 2023. SERPINA12 promotes the tumorigenic capacity of HCC stem cells through hyperactivation of AKT/β-catenin signaling. In Hepatology (Baltimore, Md.), 78, 1711-1726. doi:10.1097/HEP.0000000000000269. https://pubmed.ncbi.nlm.nih.gov/36630996/

2. Kurowska, Patrycja, Mlyczyńska, Ewa, Dawid, Monika, Dupont, Joelle, Rak, Agnieszka. 2021. Review: Vaspin (SERPINA12) Expression and Function in Endocrine Cells. In Cells, 10, . doi:10.3390/cells10071710. https://pubmed.ncbi.nlm.nih.gov/34359881/

3. Heiker, John T. 2014. Vaspin (serpinA12) in obesity, insulin resistance, and inflammation. In Journal of peptide science : an official publication of the European Peptide Society, 20, 299-306. doi:10.1002/psc.2621. https://pubmed.ncbi.nlm.nih.gov/24596079/

4. Mohamad, Janan, Sarig, Ofer, Malki, Liron, Samuelov, Liat, Sprecher, Eli. 2020. Loss-of-Function Variants in SERPINA12 Underlie Autosomal Recessive Palmoplantar Keratoderma. In The Journal of investigative dermatology, 140, 2178-2187. doi:10.1016/j.jid.2020.02.030. https://pubmed.ncbi.nlm.nih.gov/32247861/