Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025117
Hepatocellular carcinoma (HCC) represents a significant global health challenge due to its aggressive malignancy. Abnormal glycosylation is a frequent phenomenon in tumor cells and manifests as alterations in key cancer biomarkers. This phenomenon is driven primarily by changes in the expressions of glycosyltransferases. Our study focuses on GALNT7, a member of the GALNT glycosyltransferase family, which catalyzes the initiation of O-linked glycan synthesis by transferring N-acetylgalactosamine (GalNAc) to serine or threonine residues on target proteins. We observe that GALNT7 expression is notably increased in HCC tissues and is correlated with increased tumor cell invasion, migration, and proliferation, alongside with reduced apoptosis, both in vivo and in vitro. Further molecular analyses indicate that GALNT7 specifically modifies the O-glycosylation pattern of MUC13, thereby influencing the activation of the PI3K/AKT signaling pathway. Additionally, elevated GALNT7 level enhances resistance to lenvatinib-based chemotherapy regimens. Thus, GALNT7 is a critical regulator of oncogenic processes in HCC. Targeting the GALNT7-MUC13-PI3K/AKT axis represents a novel therapeutic strategy for combating HCC.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261625
Sterol biosynthesis in Stellaria dichotoma var. lanceolata remains poorly characterized despite the medicinal value of its sterol constituents. This study integrated high-performance liquid chromatography (HPLC) quantification of sterols across root, stem, leaf, and flower tissues with full-length transcriptome sequencing and comparative transcriptomics. A total of 372,483 high-quality full-length transcripts were assembled, of which 128,646 were annotated. Differential expression analysis revealed 43,354 genes shared across all four tissues (50.02% of total genes), with 9,647 differentially expressed genes (DEGs) between root and flower, 12,143 between root and leaf, and only 388 between leaf and stem. Weighted gene coexpression network analysis (WGCNA) identified 43 coexpression modules, and the MEblue module contained six key enzyme genes: NP_NY_transcript_168676 (FPPS), NP_NY_transcript_335811 (SQS), NP_NY_transcript_44001 (SQS), NP_NY_transcript_246835 (CAS), NP_NY_transcript_328932 (CAS), and NP_NY_transcript_183565 (GPPS). RT-qPCR validation confirmed expression trends consistent with transcriptome data. These findings provide a foundation for elucidating the biosynthetic pathway and molecular regulation of sterols in S. dichotoma var. lanceolata.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21593
BACKGROUND: Intervertebral disc degeneration is a core pathological mechanism of discogenic diseases, characterized by an imbalance in extracellular matrix metabolism. Tissue inhibitors of metalloproteinases, as endogenous antagonists of matrix metalloproteinases, play a crucial role in regulating extracellular matrix homeostasis, but the specific functions of subtypes, signaling pathway interactions, and epigenetic regulatory mechanisms have not been systematically clarified. OBJECTIVE: To review the expression changes, functional heterogeneity, and regulatory networks of tissue inhibitors of metalloproteinases in intervertebral disc degeneration, focusing on the molecular mechanisms and signaling pathways in oxidative stress, mechanical load, and inflammatory microenvironment, and to evaluate the translational potential of gene therapy strategies based on tissue inhibitors of metalloproteinases. METHODS: The first author searched PubMed, Web of Science, Embase, CNKI, Wanfang and other databases from inception to March 2025. Chinese search terms included '椎间盘退变，椎间盘退行性变，椎间盘退化，金属蛋白酶类组织抑制剂，信号通路', and English search terms included 'Tissue Inhibitor of Metalloproteinases, Tissue Inhibitor of Metalloproteinase, TIMPs, Intervertebral disc degeneration, Disc degeneration, Degenerative Disc Disease, Degenerative Intervertebral Discs'. Finally, 76 eligible articles were included for review. RESULTS AND CONCLUSION: (1) Subtype functions of tissue inhibitors of metalloproteinases: TIMP1 exhibits dual regulation (early protection/late depletion); TIMP2 maintains extracellular matrix homeostasis by inhibiting matrix metalloproteinase activity, and its abnormal expression can activate pro-apoptotic signaling pathways (e.g., miR-185-5p/MMP2 axis and inflammatory factor-mediated MMP/TIMP imbalance); TIMP3 exerts multi-dimensional protective effects by inhibiting matrix metalloproteinase activity, tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha axis, and angiogenesis; TIMP4 is regulated by miR-155-5p/fibroblast growth factor 2 and participates in extracellular matrix homeostasis. (2) Epigenetic reprogramming mechanisms: Abnormal mechanical stress degrades TIMP3 mRNA through the WTAP/YTHDF2-m6A axis, while miR-222 targets TIMP3 to synergistically accelerate extracellular matrix degradation. (3) Multi-modal therapeutic strategies: Photobiomodulation (wavelength-specific regulation of TIMP/MMP), stem cell exosomes (miR-199a/GREM1 axis), and irisin intervention can remodel matrix metabolic balance. This review summarizes the theoretical framework of 'functional network imbalance of tissue inhibitors of metalloproteinases', revealing its multi-level regulatory characteristics as a core driver of intervertebral disc degeneration, and providing a theoretical basis for developing precise therapies targeting epigenetic modifications and mechano-biological coupling interventions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026036
Forkhead box protein M1 (FOXM1) is a key transcription factor that regulates cell cycle progression and is frequently overexpressed in human cancers, driving tumor proliferation and therapy resistance. FOXM1 recognizes the canonical forkhead response element (FKH motif, RYAAAYA) through its conserved DNA-binding domain (DBD). Here, we report the high-resolution crystal structure of the FOXM1-DBD in complex with a double-stranded DNA substrate containing two FKH motifs. The structure reveals that FOXM1-DBD adopts the canonical winged-helix fold, with the third α-helix (α3) inserted into the DNA major groove to mediate sequence-specific recognition. Within this helix, Asn283, Arg286, and His287 form an essential triad that engages DNA bases through specific hydrogen bonds and hydrophobic interactions. Using structure-guided mutagenesis of key DNA-interacting residues combined with biophysical validation by isothermal titration calorimetry (ITC) and DNA binding assessment via electrophoretic mobility shift assay (EMSA), we confirm the functional importance of these residues and uncover position-dependent tolerance to base substitutions within the FKH motif. Furthermore, we demonstrate that FOXM1 overexpression promotes cell proliferation and upregulates the transcription of target genes in a DBD-dependent manner. Our findings provide a structural basis for understanding the DNA recognition mechanism of FOXM1 and offer mechanistic insights into how FOXM1 selectively binds to its genomic targets to regulate transcription.