PSIP1 (PC4 And SFRS1 Interacting Protein 1)

Notably, high transcript expression of a GR-LEDGF/p75-HSP27 gene panel correlated with worse overall survival in PCa patients (n = 4259). These findings identified this axis as a driver of PCa drug cross-resistance and promising therapeutic target for overcoming treatment failure.

Conversely, overexpression of PSIP1 facilitated R-loop resolution and reduced DNA damage induced by cisplatin. In conclusion, we developed a novel RGPSM that effectively predicted the outcomes of OS patients across diverse cohorts and identified PSIP1 as a critical modulator of OS progression by regulating R-loop accumulation and DNA damage.

Inhibition of guanine nucleotide biosynthesis or rRNA transcription further suppresses MLLr AML when combined with a menin inhibitor. Our findings underscore the requirement of guanine nucleotide biosynthesis in maintaining the function of the LEDGF/menin/MLL-fusion complex and provide a rationale to target guanine nucleotide biosynthesis to sensitize MLLr leukemias to menin inhibitors.

This study confirms the upregulation of LEDGF/p75 in CRC and shows its correlation with KRAS and MSH2 mutations. The interaction of LEDGF/p75 with DNA damage response proteins may contribute to drug resistance and increased tumor aggressiveness. LEDGF/p75's potential as a prognostic biomarker independent of lymph node involvement or CEA levels highlights its potential in personalized therapy, and warrants further research into its therapeutic targeting.

Our work suggests that PSIP1 promotes resistance to GR in LUAD cells by inducing the expression of WASF3 and its downstream regulator ITGB3.

New diagnostic options using HEp-2 cells with overexpression of LEDGF/p75 or mitochondrial DNA as autoimmune targets could be used to identify BPH patients with autoimmune responses. Given the presumed involvement of autoimmune responses in BPH and the efficacy of immunosuppression in reducing BPH symptoms, BPH or subvariants of BPH may be candidates for a new autoimmune disease in males.

GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression...The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR-LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.

In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.