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Activation of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway induces glial differentiation of glioblastoma (GBM) cells, but the mechanism by which microRNA (miRNA) regulate this process remains poorly understood. In this study, by performing miRNA genomics and loss‐ and gain‐of‐function assays in dibutyryl‐cAMP‐treated GBM cells, we identified a critical negative regulator, hsa‐miR‐1275, that modulates a set of genes involved in cancer progression, stem cell maintenance, and cell maturation and differentiation. Additionally, we confirmed that miR‐1275 directly and negatively regulates the protein expression of glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. Of note, tri‐methyl‐histone H3 (Lys27) (H3K27me3), downstream of the PKA/polycomb repressive complex 2 (PRC2) pathway, accounts for the downregulation of miR‐1275. Furthermore, decreased miR‐1275 expression and induction of GFAP expression were also observed in dibutyryl‐cAMP‐treated primary cultured GBM cells. In a patient‐derived glioma stem cell tumor model, a cAMP elevator and an inhibitor of H3K27me3 methyltransferase inhibited tumor growth, induced differentiation, and reduced expression of miR‐1275. In summary, our study shows that epigenetic inhibition of miR‐1275 by the cAMP/PKA/PRC2/H3K27me3 pathway mediates glial induction of GBM cells, providing a new mechanism and novel targets for differentiation‐inducing therapy. [ABSTRACT FROM AUTHOR]

Pleurotus eryngii has been widely cultivated in China and massive spent mushroom substrate (SMS) has been discarded. To utilize spent substrate of P. eryngii effectively, SMS was extracted by hot alkali liquor and a high yield (12.18%) of crude polysaccharide (designated as CPS) was obtained, then a polysaccharide-protein complex (RPS) was purified from CPS. Molecular characterization detected by size exclusion chromatography/multi-angle laser light scattering (SEC-MALLS) showed that the weight average molar mass ( M w ) of RPS was 8.372 × 10 6 g/mol. The molecular conformation of RPS was revealed to be a rigid rod form in aqueous solution. Monosaccharide composition analysis by GC–MS confirmed that RPS is a novel acid heteropolysaccharide and mainly composed of xylose, glucose, and arabinose. Then, FT-IR spectral analysis of RPS revealed prominent characteristic polysaccharide and protein groups. Pharmacological experiments in vitro suggested that both CPS and RPS exhibited strong antioxidant activities in a dose dependent manner, using different in vitro models like ABTS, superoxide, hydroxyl and DPPH. The high-yield crude polysaccharide showed potential for application as strong antioxidant in food industry. The study provided a reliable approach for spent resource recovery, which would be significant to sustainable development of mushroom industry and environmental protection. [ABSTRACT FROM AUTHOR]