Scgb3a1, also known as UGRP2 and HIN-1, is a member of the secretoglobin gene superfamily encoding a small-molecular-weight secretory protein. It has been suggested to possess tumor-suppressor function [4,5,6]. The gene is highly expressed in the lung and trachea in both humans and mice, and its expression is regulated by the transcription factor NF-Y and associated with CpG methylation in the promoter region [4].

In mouse models, the lack of Scgb3a1 did not affect the expression of other Scgb genes or the development of pulmonary neuroepithelial bodies during embryogenesis [1]. In smoking-related lung cancer, the down-regulation of Scgb3a1 was identified, and high expression of it was associated with a favorable prognosis, suggesting its potential role in this disease [2]. In interstitial lung abnormalities, SCGB3A1 protein was significantly associated with the condition, indicating its possible role as a biomarker [3].

In conclusion, Scgb3a1 plays important roles in lung-related physiological and disease processes. Mouse gene-knockout models have contributed to understanding that it may not have a major impact on the expression of related genes and the development of certain lung-related structures during embryogenesis. Its dysregulation is associated with smoking-related lung cancer and interstitial lung abnormalities, providing potential directions for disease diagnosis and treatment [1,2,3].

References:

1. Naizhen, Xu, Kido, Taketomo, Yokoyama, Shigetoshi, Linnoila, R Ilona, Kimura, Shioko. 2019. Spatiotemporal Expression of Three Secretoglobin Proteins, SCGB1A1, SCGB3A1, and SCGB3A2, in Mouse Airway Epithelia. In The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 67, 453-463. doi:10.1369/0022155419829050. https://pubmed.ncbi.nlm.nih.gov/30768367/

2. Liang, Chen, Pan, Wei, Zhou, Zhijun, Liu, Xiaomin. 2024. Identification of prognostic biomarkers of smoking-related lung cancer. In Journal of thoracic disease, 16, 1438-1449. doi:10.21037/jtd-23-1890. https://pubmed.ncbi.nlm.nih.gov/38505085/

3. Axelsson, Gisli Thor, Gudmundsson, Gunnar, Pratte, Katherine A, Emilsson, Valur, Gudnason, Vilmundur. . The Proteomic Profile of Interstitial Lung Abnormalities. In American journal of respiratory and critical care medicine, 206, 337-346. doi:10.1164/rccm.202110-2296OC. https://pubmed.ncbi.nlm.nih.gov/35438610/

4. Tomita, Takeshi, Kimura, Shioko. 2008. Regulation of mouse Scgb3a1 gene expression by NF-Y and association of CpG methylation with its tissue-specific expression. In BMC molecular biology, 9, 5. doi:10.1186/1471-2199-9-5. https://pubmed.ncbi.nlm.nih.gov/18194566/

5. Lind, G E, Skotheim, R I, Fraga, M F, Esteller, M, Lothe, R A. . Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1). In The Journal of pathology, 210, 441-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17029216/

6. Mazumdar, Jolly, Hickey, Michele M, Pant, Dhruv K, Simon, M Celeste, Keith, Brian. 2010. HIF-2alpha deletion promotes Kras-driven lung tumor development. In Proceedings of the National Academy of Sciences of the United States of America, 107, 14182-7. doi:10.1073/pnas.1001296107. https://pubmed.ncbi.nlm.nih.gov/20660313/