SETD5 (SET Domain Containing 5)

In DDLPS, high SETD5 expression in the dedifferentiated component correlated with worse overall survival (p < 0.001) but was not correlated with disease-free survival (p = 0.086). Immunohistochemical expression of SETD5 significantly correlates with prognosis in DDLPS and may serve as a candidate pathological factor for dedifferentiation and prognosis.

Its inhibition sensitizes glioma cells to TRAIL-induced apoptosis, identifying SETD5 as a potential therapeutic target. Targeting SETD5 could represent a novel strategy to overcome TRAIL resistance and enhance the efficacy of GBM therapies.

Moreover, the methylation of LC3B facilitates OC cell migration by inhibiting autophagy. Overall, our study defines a novel modification of LC3B and unveils a SETD5-mediated methylation-dependent regulatory mechanism controlling nuclear LC3B function in autophagy and migration in OC cells, offering potential therapeutic targets for OC.

The findings emphasize that SETD5 may serve as a promising indicator of stemness in NSCLC, which can help develop therapeutic targets for NSCLC and prognostic evaluation. This study provides evidence that SETD5 as H3K36me3 facilitates the m6A modification of METTL14 and the recruitment of YTHDF1 and mediates the nuclear translocation of PKM2, regulating GPX4 mediated ferroptosis resistance and SOX9 mediated stemness, causing tumor metastasis and adverse prognosis in patients.

SF3B4 contributes to HCC progression by directly binding mRNAs and interacting with proteins, thereby regulating gene expression and alternative splicing.

Our findings expand the spectrum of USP6 gene fusion partners in nodular fasciitis and, for the first time, report cases with conventional morphology exhibiting aggressive behavior, including death. These observations raise the question of whether a subset of deep lesions with conventional nodular fasciitis histology but unusual clinical features, such as large tumor size, represents malignant nodular fasciitis or alternatively a nodular fasciitis-like myofibroblastic sarcoma.

This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85βPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.

Mechanistically, by blocking PI3K/AKT/mTOR pathway with BEZ235, the effects of SETD5 overexpression on cell viability and Nanog and Sox2 protein expression were reversed. Our results substantiated that SETD5 functioned as an oncogene by promoting cell growth and stemness in colorectal cancer cells through activating the PI3K/AKT/mTOR signaling pathway.

Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.