Histone variants are emerging as key regulatory molecules in cancer. We report a unique role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z-interacting protein, levels of which are also elevated in melanoma. We further demonstrate that H2A.Z.2-regulated genes are bound by BRD2 and E2F1 in an H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies.
Objective: The presence of skin flora (SF) has been identified as a significant factor in the onset and progression of cutaneous melanoma (CM). However, the vast diversity and abundance of SF present challenges to fully understanding the causal relationship between SF and CM.
Methods: A Two Sample Mendelian Randomization (TSMR) analysis was conducted to investigating the causal relationship between SF and CM.
Idiopathic inflammatory myopathies (IIM) are a group of systemic autoimmune diseases characterized by muscle weakness and elevated serum creatine kinase levels. Recent research has highlighted the role of the innate immune system, particularly inflammasomes, in the pathogenesis of IIM. This review focuses on the role of inflammasomes, specifically NLRP3 and AIM2, and their associated proteins in the development of IIM.
Background: Melanoma is an aggressive skin tumor with limited therapeutic options due to rapid proliferation, early metastasis, and poor prognosis. Baicalin (BA), a natural flavonoid, shows promise in inducing ferroptosis and apoptosis but faces challenges of poor solubility and bioavailability. To address these issues, we developed a multifunctional drug delivery system: manganese-doped ZIF-8 nanoparticles (ZIF(Mn)) loaded with BA and modified with folic acid (FA) and polyethylene glycol (PEG).
Context.—: Patients with melanoma can develop second tumors representing either metastases or new primary melanoma. This distinction has profound implications for management.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, 310014 Hangzhou, China; Key Laboratory of Marine Fishery Resources Employment & Utilization of Zhejiang Province, Hangzhou 310014, China. Electronic address:
Transdermal drug delivery represents a promising avenue for the treatment of dermatologic diseases, such as cutaneous melanoma and skin infections. This study involves the development of a novel therapeutic strategy that employs a skin-penetrating peptide SPACE-modified flexible liposomal chrysomycin A (CA@SPACE-LP) with a particle size of 111.5 nm.
