PDE4D (Phosphodiesterase 4D)

Both in vitro and in vivo experiments demonstrated that exosomal miR-151a-3p promotes glioma cell migration, invasion, proliferation, and epithelial‒mesenchymal transition, thereby increasing tumour aggressiveness. These findings highlight the NamiR-151a-3p/PDE4D/FAK/YAP axis as a promising therapeutic target for GBM.

miR-21-5p could target PDE4DIP and promote tumor growth of NSCLC. SORBS2 suppressed NSCLC tumorigenesis by regulating miR-21-5p/PDE4DIP signaling pathway.

Harmine exerts antitumor effects in NSCLC by inducing ferroptosis through direct targeting of PDE4D and suppression of the PI3K-Akt-Nrf2 pathway, highlighting PDE4D as a novel therapeutic target and harmine as a promising candidate for NSCLC treatment.

ERMS of the middle ear is a rare type of malignant tumor with a relatively poor prognosis. Our study indicates that the concurrence of PDE4DIP mutation and C19orf69::TPM3 gene fusion may indicate poor prognosis in middle ear EMRS, providing a potential target for subsequent individualized treatment.

This study delineates oncogenotype-specific molecular and immune imprints in lung adenocarcinoma, revealing STK11-, KRAS-, and EGFR-mutated tumors as transcriptionally and immunologically discrete ecosystems. By mapping epithelial vulnerabilities alongside immune imprints, we unveil genotype-imposed dependencies that inform the rational development of precision therapies with direct translational relevance.

Additionally, the KRAS:p.G12C/S:c.34G>T/A somatic mutation variant was detected in both GL01 and A549. This study provides a method for identifying potentially clinically-relevant genes associated with a sample's copy number aberrations and the pathways they represent, providing personalized mechanistic, prognostic, and therapeutic insights into the cancer biology of our cells.

The antinociceptive effects of TP3 were abolished by the PDE4D inhibitor rolipram, highlighting the role of PDE4D-mediated modulation of the cAMP pathway in producing these effects. These findings suggest that TP3 may be a promising therapeutic agent for treating neuropathic pain by exerting anti-inflammatory and analgesic effects through regulation of the cAMP pathway.

Depletion of PDE4DIP mislocalizes PKA RIIα from the Golgi and leads to its degradation, thereby compromising its negative regulatory effect on PKA signalling. Overall, our findings provide novel insights into the roles of the PDE4DIP-AKAP9 complex in regulating PKA signalling and NSCLC growth and highlight PDE4DIP as a promising therapeutic target for NSCLC.

In summary, our research showed that PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors and suggests that PDE4 inhibition is a novel therapeutic option for treatment of BRAF-mutated melanoma patients.

Considering significantly lower gene expression, aligned with our immunohistochemical data in tumor tissue in comparison to the control tissue, as well as the significantly poorer survival rate in the case of its higher expression, we can hypothesize that SFRP5 is the most promising biomarker for CRC out of the observed proteins. These findings suggest alterations in PDE4B, PDE4D, and SFRP5 expression during CRC progression, as well as between different stages of CRC, with potential implications for understanding the molecular mechanisms involved in CRC development and progression.

Overall, we identified LINC00152 inhibition as a novel mechanism of tamoxifen sensitization via restoring tamoxifen-dependent ferroptosis upon destabilizing PDE4D, increasing cAMP and Ca2+ levels, thus leading to ROS generation and lipid peroxidation. Our findings reveal LINC00152 and its effectors as actionable therapeutic targets to improve clinical outcome in refractory ER+ breast cancer.

We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.