Pdcd1, which encodes PD-1, is an important gene in the immune system. PD-1 is a key immune checkpoint protein and a major immunotherapy target for treating cancer [1,2]. The PD-1/PD-L1 interaction pathway is central in cancer immunology, and understanding the regulation of Pdcd1 is crucial for cancer immunotherapy strategies [2].

The PDCD1 gene can be alternatively spliced to generate an exon 3-skipped isoform PD-1Δ3, which may antagonize PD-1. Through a minigene system, two splicing enhancers (ESE3a and ESE3b) in exon 3 were mapped, and MATR3 was defined as a splicing activator during PDCD1 exon 3 splicing, with its activity counteracted by an RNA secondary structure and an RNA helicase DDX5. Additionally, ASOs were identified that can promote PDCD1 exon 3 skipping, potentially serving as drug candidates for cancer treatment [1]. Single-nucleotide polymorphisms (SNPs) of PDCD1 are associated with the susceptibility to multiple myeloma, and specific genotypes affect the clinical features of multiple myeloma patients [3]. In ankylosing spondylitis, the promoter of PDCD1 is hypermethylated, and its mRNA expression is downregulated, with a significant negative correlation between DNA methylation and mRNA expression [4]. PDCD1 may also be a candidate diagnostic biomarker for acute kidney transplant rejection as shown by comprehensive bioinformatic analysis [5].

In summary, Pdcd1 plays a vital role in immune regulation, especially in cancer immunology. Studies on its alternative splicing, genetic polymorphisms, epigenetic regulation, and potential as a biomarker in various diseases have provided valuable insights. Understanding Pdcd1's functions through different research models helps in developing better strategies for cancer treatment and diagnosis of other diseases such as ankylosing spondylitis and acute kidney transplant rejection.

References:

1. Sun, Junjie, Bai, Jialin, Jiang, Tao, Gao, Yuan, Hua, Yimin. 2019. Modulation of PDCD1 exon 3 splicing. In RNA biology, 16, 1794-1805. doi:10.1080/15476286.2019.1659080. https://pubmed.ncbi.nlm.nih.gov/31441370/

2. Mishra, Alok, Verma, Mukesh. . Epigenetic and Genetic Regulation of PDCD1 Gene in Cancer Immunology. In Methods in molecular biology (Clifton, N.J.), 1856, 247-254. doi:10.1007/978-1-4939-8751-1_14. https://pubmed.ncbi.nlm.nih.gov/30178256/

3. Kasamatsu, Tetsuhiro, Awata, Maaya, Ishihara, Rei, Saitoh, Takayuki, Murakami, Hirokazu. 2019. PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma. In Clinical and experimental medicine, 20, 51-62. doi:10.1007/s10238-019-00585-4. https://pubmed.ncbi.nlm.nih.gov/31620907/

4. Wu, Ye, Chen, Yuting, Sun, Xiaoya, Ni, Man, Pan, Faming. 2023. DNA methylation and transcriptome signatures of the PDCD1 gene in ankylosing spondylitis. In Genes and immunity, 24, 46-51. doi:10.1038/s41435-023-00196-w. https://pubmed.ncbi.nlm.nih.gov/36707702/

5. Wang, Yucheng, Lin, Xiaoli, Wang, Cuili, Chen, Jianghua, Huang, Hongfeng. 2023. Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis. In Frontiers in immunology, 13, 1076546. doi:10.3389/fimmu.2022.1076546. https://pubmed.ncbi.nlm.nih.gov/36776400/