Growth is an important trait in aquaculture that is influenced by various factors, among which genetic regulation plays a crucial role. Megalobrama amblycephala, one of the most important freshwater species in China, exhibits wide variations in body mass among individuals of the same age within the same pool. But the molecular mechanisms underlying wide variation in body mass remain unclear. Here, we performed muscle histological and transcriptome analysis of muscle tissues from Fast-Growing (FG) and Slow-Growing (SG) M. amblycephala at the age of 4 months old (4 mo) and 10 months old (10 mo) to elucidate its muscle development and growth mechanism. The muscle histological analysis showed smaller diameter and higher total number of muscle fibers in FG compared to SG at 4 mo, while larger diameter and total number of muscle fibers were detected in FG at 10 mo. The transcriptome analysis of muscle tissue detected 1171 differentially expressed genes (DEGs) between FG and SG at 4 mo, and 718 DEGs between FG and SG at 10 mo. Furthermore, 44 DEGs were consistently up-regulated in FG at both 4 mo and 10 mo. Up-regulated DEGs in FG at 4 mo were mainly enriched in the pathways related to cell proliferation, while down-regulated DEGs were significantly enriched in cell fusion and muscle contraction. Up-regulated DEGs in FG at 10 mo were mainly enriched in the pathways related to cell proliferation and protein synthesis. Therefore, these results provide novel insights into the molecular mechanism of M. amblycephala muscle growth at different stages, and will be of great guiding significance to promote the fast growth of M. amblycephala.

Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), remains one of the most aggressive primary brain tumors, and its proteostasis machinery represents a potential therapeutic target. Here we identify HSP27 as a key regulator-associated proteostasis in glioblastoma, IDH-wildtype, where it is linked to protein synthesis, folding, stress-granule dynamics and ubiquitin-mediated turnover. Ribo-seq showed HSP27 depletion reduced global protein synthesis, while TME labeling coupled to mass spectrometry revealed increased accumulation of unfolded proteins, indicating proteotoxic stress. Proteomic analysis of isolated stress granules (SGs) revealed enhanced sequestration of translational regulators, including EIF4E, mTOR, EIF3M and QKI, into stress granules (SGs), thereby reinforcing translational repression. Ubiquitinome profiling further revealed increased ubiquitination and proteasome-dependent loss of oncogenic and translational regulators, including AKT2, PARP1, EIF4G1, EIF4A3, and DDX5. Functionally, targeting HSP27 inhibits tumor growth and sensitizes glioblastoma to translational blockade. In orthotopic models, antisense oligonucleotide targeting HSP27 in combination with Didemnin B suppressed tumor progression and prolonged survival compared with either single agent. These findings associate HSP27 with proteostasis in glioblastoma, IDH-wildtype, and suggest HSP27-dependent proteostasis buffering as a therapeutic vulnerability.