Transcription Factor 21 Inhibits Prostate Cancer Progression via Transcriptional Repression of PSAT1

Transcriptional regulation plays a critical role in the molecular pathogenesis and progression of prostate cancer (PCa). This study explores the regulatory role of the transcription factor 21 (TCF21)/phosphoserine aminotransferase 1 (PSAT1) axis in AKT signaling during PCa progression. Bioinformatics analysis identified PSAT1 as significantly upregulated in PCa cells, which was further confirmed by RT-qPCR and Western blotting. Functional assays demonstrated that knockdown of PSAT1 suppressed proliferation, migration, and invasion while promoting apoptosis in PCa cells. PSAT1 knockdown reduced phosphorylation of AKT, suggesting its involvement in AKT pathway activation. Notably, treatment with an AKT inhibitor diminished the tumor-promoting effects of PSAT1 overexpression, reinforcing the link between PSAT1 and AKT signaling. Upstream regulation of PSAT1 was investigated, revealing that TCF21 was downregulated in PCa and negatively regulated PSAT1 expression. TCF21 directly repressed PSAT1 at the transcriptional level by binding to its promoter. Furthermore, PSAT1 overexpression led to a partial reversal of the inhibitory effects of TCF21 overexpression on malignant phenotypes in PCa cells. These findings suggest that TCF21 suppresses PCa malignancy by downregulating PSAT1 and inhibiting AKT pathway activity.