Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a complex pathogenesis that was previously thought to involve primarily adaptive immunity. Emerging evidence underscores the role of neutrophils in shaping immune dysregulation and inducing organ damage in lupus. This study aims to investigate the dynamics of neutrophil senescence and its relationship with lupus, an area that remains poorly understood. Here, we identify a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in the peripheral blood of SLE patients compare to that in the healthy donors. Increased numbers of senescence-like neutrophils are positively correlated with SLE disease activity and autoantibody production in SLE patients. In addition, senescence-like neutrophils derived from SLE patients exhibit an impaired ability to suppress the proinflammatory activity of natural killer (NK) cells and CD4+ T cells. Further mechanistic exploration suggests that these senescence-like neutrophils might exert their immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results demonstrate that senescence-like neutrophils could serve as biomarkers for assessing the disease activity of SLE. The compromised immunosuppressive function of senescence-like neutrophils provides a new perspective on SLE pathophysiology and may pave the way for the development of novel therapies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025207
O-GlcNAcylation, a prevalent reversible post-translational modification, intricately alters non-histone proteins, influencing the organization of gene transcriptional regulation within the accessible chromatin environment. This nucleoplasmic landscape, characterized by histone-free regions, fundamentally enables O-GlcNAc-mediated modulation through dynamic accessibility. However, unraveling the O-GlcNAc-open chromatin interplay that governs sophisticated transcriptional regulatory networks remains constrained by current techniques, which lack the resolution to probe this spatiotemporal crosstalk. Here, we report a general strategy to systematically and chemoselectively profile O-GlcNAc-associated chromatin accessibility on a genome-wide scale (COCA-seq). Through comprehensive validation across low- and high-throughput levels, we demonstrate COCA-seq’s dual fidelity in both O-GlcNAc chemoselectivity and open chromatin specificity. We employ it to delve into doxorubicin resistance for breast cancer, scrutinizing pivotal regulatory genes and transcription factors implicated in this complex biological event. By integrating bulk RNA-seq with COCA-seq, we offer a multiomics perspective, shedding light on related biological processes and pathways like drug efflux and stress homeostasis, thereby uncovering potential mechanisms by which O-GlcNAc-associated open chromatin orchestrates tumor drug resistance. COCA-seq emerges as a general and versatile tool across various biological contexts, poised to reveal the landscape of O-GlcNAc-associated open chromatin regions across the genome and decipher the significance of glycosylation behind it.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025141
Colorectal cancer (CRC) is a common type of gastrointestinal malignancy, and it has a close connection with long noncoding RNAs (lncRNAs). This study aims to examine the involvement of long noncoding RNA LINC00114, which targets heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) in regulating glutamine metabolism and angiogenesis in the metastasis of colorectal cancer (CRC). LINC00114 and HNRNPA1 levels are measured in CRC tissues and cells to determine their expression levels. Then, siRNA targeting LINC00114 (si-LINC00114) is used to transfect CRC cells, and cell proliferation and metastasis are detected. The influence of exogenous glucose and glutamine supplementation on angiogenesis induced by LINC00114 in CRC is investigated in HUVECs. Glutamine metabolism in CRC cells is also detected. Furthermore, the role of LINC00114 in CRC xenograft tumors is studied in vivo. LINC00114 and HNRNPA1 are highly expressed in CRC and positively correlate with CD31. si-LINC00114 significantly inhibits proliferation, metastasis and HNRNPA1 expression in CRC cells. An RNA-binding-protein immunoprecipitation (RIP) assay confirms that LINC00114 can bind to HNRNPA1 and positively regulate its expression. Further experiments confirm that si-LINC00114 significantly inhibits cell proliferation and tubule formation in HUVECs. Exogenous glucose and glutamine supplementation significantly promotes the levels of LINC00114 and HNRNPA1 in CRC cells and promotes tubule formation in HUVECs. In addition, transfection of CRC cells with si-LINC00114 and/or oe-HNRNPA1 regulates glutamine metabolism in CRC cells. Animal studies confirm that intervention with LINC00114 represses the progression and vascular normalization of CRC and regulates glutamine metabolism. In conclusion, LINC00114 promotes CRC metastasis by targeting HNRNPA1 to regulate glutamine metabolic reprogramming and angiogenesis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024139
Esophageal cancer (EC) is one of the most recalcitrant cancers, with a 5-year survival rate of < 30%. The hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) plays an essential role in long-chain fatty acid metabolism, and dysregulation of HADHA has been demonstrated to be involved in a series of metabolic diseases and cancers. However, its role in cancers remains controversial. HADHA has seldom been investigated in EC, and little is known about how HADHA regulates the malignant progression of EC. In this study, we find that HADHA is significantly upregulated in EC tissues and is correlated with poor survival. HADHA knockdown markedly inhibits EC cell proliferation both in vitro and in vivo. The loss of HADHA also induces EC cell apoptosis, causes cell cycle arrest and inhibits cell migration. Additionally, RNA profiling reveals that mTOR signaling is significantly suppressed after HADHA knockdown. Mechanistically, HADHA interacts with SP1 and induces MDM2 expression. In conclusion, both mTOR signaling and the SP1-MDM2 axis participate in the HADHA-induced malignant behavior of EC cells.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025141
Colorectal cancer (CRC) remains the third most common malignancy and second leading cause of cancer-related mortality, with metastasis accounting for the majority of deaths. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumor progression, yet the mechanistic basis of their involvement in CRC metabolic reprogramming and angiogenesis is incompletely defined. This study investigates the role of LINC00114 in CRC metastasis, focusing on its interaction with heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and downstream effects on glutamine metabolism and angiogenesis. LINC00114 and HNRNPA1 were found to be highly expressed in CRC tissues and cells, positively correlating with CD31. siRNA-mediated silencing of LINC00114 (si-LINC00114) significantly inhibited CRC cell proliferation, metastasis, and HNRNPA1 expression. RNA-binding protein immunoprecipitation confirmed direct binding of LINC00114 to HNRNPA1, with positive regulation of HNRNPA1 expression. In HUVECs, si-LINC00114 suppressed proliferation and tubule formation. Exogenous glucose and glutamine supplementation promoted LINC00114 and HNRNPA1 levels in CRC cells and enhanced HUVEC tubule formation, with glutamine exerting a greater effect than glucose. Transfection with si-LINC00114 and/or oe-HNRNPA1 modulated glutamine metabolism in CRC cells. In vivo, LINC00114 intervention repressed tumor progression, vascular normalization, and glutamine metabolism. These findings establish LINC00114 as a promoter of CRC metastasis through HNRNPA1-mediated glutamine metabolic reprogramming and angiogenesis, suggesting potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex pathogenesis historically attributed to adaptive immunity. Emerging data implicate neutrophils in immune dysregulation and organ damage. This study investigates neutrophil senescence dynamics in SLE. We identified a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in peripheral blood of SLE patients versus healthy donors. Increased senescence-like neutrophil numbers positively correlated with SLE disease activity and autoantibody production. Functionally, senescence-like neutrophils from SLE patients exhibited impaired suppression of proinflammatory activity in natural killer (NK) cells and CD4+ T cells. Mechanistically, these cells may exert immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results position senescence-like neutrophils as candidate biomarkers for SLE disease activity. The compromised immunosuppressive function of these cells offers a new perspective on SLE pathophysiology and may inform development of novel therapies. Limitations include small sample size and heterogeneous treatment backgrounds, necessitating further validation. Future studies will address NET release and potential subset markers.