DLX4 promotes the expression of PD-L1 through GATA1 in Gestational Trophoblastic Neoplasia

Abstract

Gestational Trophoblastic Neoplasia (GTN) is a highly malignant tumor that originates from trophoblastic cells during embryonic development. In this study, we observed that DLX4, a member of the Distal-Less Homeobox (Dlx) gene family, was upregulated in GTN tissues and cell lines. Bioinformatic analysis showed that DLX4 was highly expressed in most cancers and had a poor survival prognosis in certain tumors; further analysis showed that DLX4 was significantly associated with genes of immune pathways and immune infiltration. Functional analyses revealed that DLX4 overexpression or knockdown did not affect GTN cell proliferation; however, we observed that DLX4 could regulate PD-L1 expression via GATA1. The luciferase reporter activity of the wild-type construct increased after overexpression of GATA1, whereas the mutation of the binding sites abolished the transcriptional increase. In conclusion, our findings suggest that DLX4 regulates PD-L1 expression via GATA1 in GTN and may be a new target for antitumor therapy.