PLCB4 (Phospholipase C Beta 4)

This study's integrative approach-combining target identification, pathway inference, and in silico drug screening-offers a promising framework for rational drug development in GBM. The findings may reduce unnecessary experimental screening and medical costs, and represent a significant step toward improving therapeutic outcomes and prognosis for GBM patients.

Furthermore, we explore the multifaceted roles of PI-PLCs in signal transduction, cellular homeostasis, and membrane dynamics, whilst highlighting the intricate regulatory mechanisms governing their activity such as protein-protein interactions, post-translational modifications, and lipid modulation. Lastly, we assess the involvement of PI-PLCs in various diseases, such as cancer, neurological disorders, immune dysregulation, and male infertility, emphasizing their potential as therapeutic targets.

Moreover, experiments conducted in nude mice indicated that BRD4 inhibitor, (+)-JQ1 decreased the expression of AR-related genes and inhibited OS cell growth in vivo. In conclusion, elevated expression of BRD4 in OS cells induced by androgens participates in AR-related transcriptional regulatory processes, facilitating the malignant progression of OS.

New compounds exhibiting significant inhibitory activity against PI-PLC have been identified. The findings could prove valuable in the development of clinically applicable PI-PLC inhibitors, particularly for the treatment of cancer. Additionally, the myo-inositol derivatives developed demonstrated greater suitability for studying PI-PLC's role in physiological processes in tissue homogenates compared to the maleimide derivative U73122, which is commonly used for this purpose in scientific research. This advantage arises from the fact that U73122 is a non-specific 'pan-assay interference compound' (PAIN).

This proof-of-concept study shows that substantial amounts of DNA could be detected in vitreous fluids from uveal melanoma patients, including melanoma-cell derived DNA in 69% of the samples. Prognostically-relevant genetic alterations of the primary tumour could be identified in 45% of the patients. A follow-up study is needed to evaluate our approach in a prospective clinical context. Additionally, our work highlights improved possibilities to sensitively analyse scarce and heterogeneous tumour biopsies, with potential application in other malignancies.

Oncogenetic and likely oncogenetic variants were found in the ATM, BRCA1, PTEN, KMT2D, and CDH1 genes. Moreover, variants of uncertain significance were found in ATM, DDR2, FANCA, FOXA1, PLCB4, PTCH1, and RB1.

In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.

The results showed that the involvement of UM-related Wnt/β-catenin and Chemokine signaling pathways and the ceRNA regulatory axes showed noteworthy interest in UM metastasis.

Differences in the expression of CDKN2A, PLCB4, and NXPE4 across various CRC tissues and cells were characterized using WB, IHC and qRT-PCR. This study not only highlights the diverse omics profiles of CRGs in CRC but also introduces a novel model for accurate prognostic forecasting.

Our results demonstrate that a reproducible NGS-based workflow translates into a reliable tool for the clinical stratification of patients with UM.

The persistence of Pro-PrP in GSCs is an altered cellular mechanism responsible of the aberrant, constitutive activation of Wnt/β-catenin pathway, which contributes to glioblastoma malignant features. Thus, the activity of Pro-PrP may represent a targetable vulnerability in glioblastoma cells, offering a novel approach for differentiating and eradicating glioblastoma stem cells.

Notch and PI-PLC signaling facilitate intercellular communication, TGF-β promotes quiescence and suppresses hematopoiesis, and NF-κB-driven inflammatory responses foster an environment detrimental to normal hematopoiesis. This review highlights the role of these pathways within the MDS microenvironment, driving the development and progression of the disease and paving the way for new possible therapeutic strategies.