PTBP1 (Polypyrimidine Tract Binding Protein 1)

Importantly, CUL5 knockout significantly enhanced the efficacy of anti-PD-1 immunotherapy in a xenograft model. Collectively, these findings reveal a novel mechanism of bladder cancer immune evasion, providing potential targets for cancer immunotherapy.

These findings collectively demonstrate that PTBP1 is overexpressed in BC and drives cancer-specific metabolic reprogramming associated with the Warburg effect. Therefore, PTBP1 may act as an oncogenic regulator of breast cancer metabolism and serve as a potential therapeutic target.

Inhibition of the PTBP1-TRAF6 pathway alleviated lung injury, restored macrophage polarization balance, and promoted NETs clearance. PTBP1 enhances TRAF6 expression by stabilizing its mRNA, promoting M1 macrophage polarization and impairing NETs clearance, ultimately aggravating COPD.

Additionally, we found that a colon cancer-associated SNP in the POU2AF2/C11orf53 3'UTR creates an ectopic DplUSE site, increasing gene expression in zebrafish gut cells and in a human cell line. We have therefore identified a short 3'UTR motif present in diverse vertebrate genes that controls their expression through conserved RBPs interactions and is implicated in human disease.

In vivo, MSC-exo inhibited tumor growth and autophagy while promoting apoptosis in TPC-1 cell xenografts. In conclusion, MSC-Exo carrying LINC00900 can effectively inhibit tumor cell growth in TC via suppression of PTBP1.

Survival analyses revealed that co-high expression of SRSF1, HNRNPF, or PTBP1 and oncogenic MYC predicts poor clinical outcomes in MCL patients. Our data describe the clinical significance of aberrant SRSF1, hnRNP F, and PTBP1 in MCL and their tumor-promoting roles via the regulation of cancer hallmarks, which could be important in understanding MCL pathogenesis and therapeutic development.

Furthermore, we identified RBM47 and PTBP1 as key regulators that promote KRAS E4 inclusion. Our findings demonstrate that RBM47- and PTBP1-mediated alternative splicing of KRAS contributes to enhanced tumor progression, highlighting KRAS alternative splicing as a promising therapeutic target for cancer treatment.

When heterogeneous nuclear ribonucleoprotein K (hnRNPK), an ITAF for the HTLV-1 IRES but not for the sHBZ IRES, is overexpressed with HuR, HTLV-1 IRES is stimulated, whereas sHBZ IRES activity is reduced. Consequently, ITAFs or combinations of ITAFs differentially modulated the HTLV-1 IRES and sHBZ IRES activity, indicating that these IRESs are under translational control mediated by different subsets of ITAFs.

6-MF targets PTBP1 to inhibit circPIAS1 biogenesis and reduce circPIAS1-108aa.6-MF inhibits PI3K-AKT pathway; combined with IFN-γ, it enhances STAT1 phosphorylation, inhibits SLC7A11/GPX4 pathway, promoting melanoma ferroptosis. Its combination with PD-1 inhibitor enhances antitumor efficacy, providing a novel therapeutic strategy for melanoma treatment.

Mechanistic studies further indicated that PTBP1 binds to the 5' untranslated region (UTR) of solute carrier family 7 member 11 (SLC7A11) mRNA, stabilizing it and preserving SLC7A11 protein expression, thus inhibiting ferroptosis. Our study proposes a molecular mechanism by which PTBP1 promotes endometrial cancer progression by suppressing ferroptosis​​, suggesting that PTBP1 may be a promising therapeutic target for endometrial cancer.